sigma receptors

Summary

Summary: A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.

Top Publications

  1. ncbi Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival
    Teruo Hayashi
    Cellular Pathobiology Unit, Plasticity and Development Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, MD 21224, USA
    Cell 131:596-610. 2007
  2. ncbi Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems
    T P Su
    Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224
    Science 240:219-21. 1988
  3. ncbi Low density of sigma1 receptors in early Alzheimer's disease
    Masahiro Mishina
    Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    Ann Nucl Med 22:151-6. 2008
  4. pmc Regulating ankyrin dynamics: Roles of sigma-1 receptors
    T Hayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 98:491-6. 2001
  5. ncbi Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: characterization by ligand binding and photoaffinity labeling
    S B Hellewell
    Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892
    Eur J Pharmacol 268:9-18. 1994
  6. ncbi Initial identification and characterization of sigma receptors on human peripheral blood leukocytes
    S A Wolfe
    Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland
    J Pharmacol Exp Ther 247:1114-9. 1988
  7. ncbi Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders
    Teruo Hayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21209, USA
    CNS Drugs 18:269-84. 2004
  8. ncbi The sigma receptor as a ligand-regulated auxiliary potassium channel subunit
    Ebru Aydar
    Department of Physiology, School of Medicine, University of Wisconsin Madison, 1300 University Avenue, Madison, WI 53706, USA
    Neuron 34:399-410. 2002
  9. ncbi Sigma receptors and cancer: possible involvement of ion channels
    Ebru Aydar
    Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College, South Kensington Campus, London SW7 2AZ, United Kingdom
    Cancer Res 64:5029-35. 2004
  10. ncbi Identification of regions of the sigma-1 receptor ligand binding site using a novel photoprobe
    Arindam Pal
    Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA
    Mol Pharmacol 72:921-33. 2007

Detail Information

Publications219 found, 100 shown here

  1. ncbi Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival
    Teruo Hayashi
    Cellular Pathobiology Unit, Plasticity and Development Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, MD 21224, USA
    Cell 131:596-610. 2007
    ..These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival...
  2. ncbi Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems
    T P Su
    Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224
    Science 240:219-21. 1988
    ..The findings suggest that steroids are naturally occurring ligands for sigma receptors and raise the possibility that these sites mediate some aspects of steroid-induced mental disturbances and ..
  3. ncbi Low density of sigma1 receptors in early Alzheimer's disease
    Masahiro Mishina
    Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    Ann Nucl Med 22:151-6. 2008
    ..However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET)...
  4. pmc Regulating ankyrin dynamics: Roles of sigma-1 receptors
    T Hayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 98:491-6. 2001
    ....
  5. ncbi Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: characterization by ligand binding and photoaffinity labeling
    S B Hellewell
    Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892
    Eur J Pharmacol 268:9-18. 1994
    ..These data are consistent with the notion that the 25 kDa and 21.5 kDa proteins represent sigma 1 and sigma 2 receptors, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)..
  6. ncbi Initial identification and characterization of sigma receptors on human peripheral blood leukocytes
    S A Wolfe
    Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland
    J Pharmacol Exp Ther 247:1114-9. 1988
    ..Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown...
  7. ncbi Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders
    Teruo Hayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21209, USA
    CNS Drugs 18:269-84. 2004
    ..However, it is now clear that sigma receptors are unique non-opioid, non-phencyclidine brain proteins...
  8. ncbi The sigma receptor as a ligand-regulated auxiliary potassium channel subunit
    Ebru Aydar
    Department of Physiology, School of Medicine, University of Wisconsin Madison, 1300 University Avenue, Madison, WI 53706, USA
    Neuron 34:399-410. 2002
    ..b>Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different ways in the presence and absence of ligands...
  9. ncbi Sigma receptors and cancer: possible involvement of ion channels
    Ebru Aydar
    Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College, South Kensington Campus, London SW7 2AZ, United Kingdom
    Cancer Res 64:5029-35. 2004
    ..Whereas the precise molecular mechanism(s) of sigma receptors and their involvement in cancer cell biology have not been elucidated, recent work has started to shed some ..
  10. ncbi Identification of regions of the sigma-1 receptor ligand binding site using a novel photoprobe
    Arindam Pal
    Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA
    Mol Pharmacol 72:921-33. 2007
    b>sigma Receptors, once considered a class of opioid receptors, are now regarded as a unique class of receptors that contain binding sites for a wide range of ligands, including the drug 1-N(2',6'-dimethylmorpholino)3-(4-t-butylpropylamine)..
  11. pmc Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy
    Hiroyuki Kashiwagi
    Department of Surgery, Washington University School of Medicine, Saint Louis, USA
    Mol Cancer 6:48. 2007
    ..The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis...
  12. ncbi Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer
    Zhude Tu
    Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Nucl Med Biol 32:423-30. 2005
    ..Consequently, [(11)C]2 is a potential radiotracer for imaging the proliferative status of breast tumors in vivo with PET...
  13. ncbi Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides
    Rae R Matsumoto
    Department of Pharmaceutical Sciences, P O Box 26901, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA
    Neuropharmacology 42:1043-55. 2002
    Pharmacological and molecular biological tools were used to validate the involvement of sigma receptors in the actions of cocaine...
  14. ncbi Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1)
    R Kekuda
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912 2100, USA
    Biochem Biophys Res Commun 229:553-8. 1996
    ..Several human tissues, including placenta, liver, and brain, and several human cell lines express the SigmaR1 mRNA (1.7 kb) to a variable extent...
  15. ncbi Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level
    D Dussossoy
    Sanofi Recherche, Montpellier, France Sanofi Recherche, Labege, France
    Eur J Biochem 263:377-86. 1999
    ..Taken together our results suggest that both SR31747A-binding proteins not only play a role in sterol metabolism but indirectly affect lipoprotein functions...
  16. ncbi [3H]N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methylbenzamide: a novel sigma-2 receptor probe
    Jinbin Xu
    Department of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110, USA
    Eur J Pharmacol 525:8-17. 2005
    ..The pharmacologic profile of [3H]RHM-1 was in agreement with that of [3H]DTG. The results of this study indicate that [3H]RHM-1 is a useful ligand for studying sigma2 receptors in vitro...
  17. pmc Purification, molecular cloning, and expression of the mammalian sigma1-binding site
    M Hanner
    Instit für Biochemische Pharmakologie, Universitat Innsbruck, Austria
    Proc Natl Acad Sci U S A 93:8072-7. 1996
    ..Northern blots showed high densities of the sigma1-binding site mRNA in sterol-producing tissues. This is also in agreement with the known ability of sigma1-binding sites to interact with steroids, such as progesterone...
  18. ncbi Cocaine modulates cytokine and enhances tumor growth through sigma receptors
    Brian Gardner
    Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90095, USA
    J Neuroimmunol 147:95-8. 2004
    b>Sigma receptors are intracellular receptors that interact with a variety of psychotropic ligands, including cocaine...
  19. ncbi Selective loss of cerebral cortical sigma, but not PCP binding sites in schizophrenia
    A D Weissman
    Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224
    Biol Psychiatry 29:41-54. 1991
    ..Therefore, it has been suggested that PCP and sigma receptors may be important in the clinical manifestations of schizophrenia...
  20. ncbi Purification, pharmacological characterization and photoaffinity labeling of sigma receptors from rat and bovine brain
    D I Schuster
    Department of Chemistry, New York University, New York 10003, USA
    Brain Res 670:14-28. 1995
    ....
  21. ncbi Phencyclidine and sigma receptors in rat spinal cord: binding characterization and quantitative autoradiography
    L M Aanonsen
    Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis 55455
    Synapse 4:1-10. 1989
    ..The results of the present study show that PCP and sigma receptor binding sites are differentially localized in the rat spinal cord and suggest that separate binding sites exist for PCP and sigma agonists...
  22. ncbi Delineating biochemical and functional properties of sigma receptors: emerging concepts
    T P Su
    Neurochemistry Unit, National Institute on Drug Abuse NIH, Baltimore, MD
    Crit Rev Neurobiol 7:187-203. 1993
    b>sigma Receptors have been implicated in many pharmacological and physiological functions...
  23. ncbi Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer
    Amalia Azzariti
    Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, 70125 Bari, Italy
    Mol Cancer Ther 5:1807-16. 2006
    ..In conclusion, we suggest that the sigma(2) agonist PB28 could be an interesting antitumor agent either in monotherapy or in combination with conventional drugs...
  24. ncbi Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons
    Hongling Zhang
    Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    J Neurophysiol 87:2867-79. 2002
    Studies on the expression and cellular function of sigma receptors in autonomic neurons were conducted in neonatal rat intracardiac and superior cervical (SCG) ganglia...
  25. ncbi Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation
    Marie Stampe Ostenfeld
    Apoptosis Department and Centre for Genotoxic Stress Response, Institute for Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Autophagy 4:487-99. 2008
    ..Threrefore, the combination of siramesine with inhibitors of autophagosome formation appears as a promising approach for future cancer therapy...
  26. pmc Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice
    H W Kim
    Department of Physiology, College of Medicine and Research Institute for Medical Sciences, Chungnam National University, Daejeon, South Korea
    Br J Pharmacol 154:1125-34. 2008
    ..Despite data suggesting a link between Sig-1 Rs and NMDA receptors, there are no studies addressing whether Sig-1 R activation directly affects NMDA receptor sensitivity...
  27. ncbi sigma(2) Receptors regulate changes in sphingolipid levels in breast tumor cells
    Keith W Crawford
    Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA
    Eur J Pharmacol 443:207-9. 2002
    ..Both effects were attenuated by the novel sigma(2) receptor antagonist, N-phenethylpiperidine oxalate (AC927). sigma(2) Receptors may produce effects on cell growth and apoptosis by regulating the sphingolipid pathway...
  28. ncbi In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia
    Agostino Marrazzo
    Department of Pharmaceutical Sciences, University of Catania, Italy
    Life Sci 78:2449-53. 2006
    ..c.v.) analgesia. The mechanism involved in these effects was not clear, but provided additional data on a diverging modulator role of selective sigma-1 antagonists on KOP analgesia...
  29. ncbi Differential effects of sigma1 receptor blockade on self-administration and conditioned reinstatement motivated by cocaine vs natural reward
    Remi Martin-Fardon
    Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuropsychopharmacology 32:1967-73. 2007
    ..The findings support a role for sigma(1) receptors in regulating conditioned responses to cocaine-related contextual stimuli and identify this receptor as a potential treatment target for the prevention of craving and relapse...
  30. ncbi Correlation between sigma2 receptor protein expression and histopathologic grade in human bladder cancer
    Nicola Antonio Colabufo
    Dipartimento Farmaco Chimico, Facolta di Farmacia, Universita degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy
    Cancer Lett 237:83-8. 2006
    ..Moreover, these receptors were undetected in a low-grade squamous cell carcinoma and in a very rare form of anaplastic, large cells plasmacytoid cancer...
  31. pmc Interactions between 3,4-methylenedioxymethamphetamine and sigma1 receptors
    Matthew K Brammer
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73190 USA
    Eur J Pharmacol 553:141-5. 2006
    ..Earlier studies in our laboratory have shown that methamphetamine interacts with sigma receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and ..
  32. pmc Sigma-2 receptors as a biomarker of proliferation in solid tumours
    K T Wheeler
    Department of Radiology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Br J Cancer 82:1223-32. 2000
    ....
  33. ncbi Modulation of NMDA and dopaminergic neurotransmissions by sigma ligands: possible implications for the treatment of psychiatric disorders
    G Debonnel
    Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, , , Canada
    Life Sci 58:721-34. 1996
    ..Several subtypes of sigma receptors are present in high densities in the limbic structures as well as in motor-related areas of the CNS...
  34. ncbi Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity
    Tangui Maurice
    CNRS UMR 5102, University of Montpellier II, c c 090, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France
    Neurosci Biobehav Rev 26:499-527. 2002
    ..The therapeutic potentials and neuropharmacological perspectives opened by the use of selective sigma(1) receptor antagonists in cocaine addiction will finally be discussed...
  35. ncbi Targeting sigma receptor-binding benzamides as in vivo diagnostic and therapeutic agents for human prostate tumors
    C S John
    Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA
    Cancer Res 59:4578-83. 1999
    b>Sigma receptors are known to be expressed in a variety of human tumor cells, including breast, neural, and melanoma tumors. A very high density (1.0-1...
  36. pmc Intracellular sigma1 receptor modulates phospholipase C and protein kinase C activities in the brainstem
    M P Morin-Surun
    Institut Alfred Fessard, Avenue de la Terrasse, 91198 Gif sur Yvette, France
    Proc Natl Acad Sci U S A 96:8196-9. 1999
    ..This might be an example of a mechanism by which an intracellular receptor modulates metabotropic responses...
  37. ncbi Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals
    Kenji Hashimoto
    Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
    Curr Pharm Des 12:3857-76. 2006
    b>Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system...
  38. ncbi Characterization of a novel iodinated sigma-2 receptor ligand as a cell proliferation marker
    Catherine Hou
    Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nucl Med Biol 33:203-9. 2006
    ..Further modification of the ligand and the imaging parameters will be needed to improve the signal for in vivo detection...
  39. pmc Sigma receptors: potential targets for a new class of antidepressant drug
    James A Fishback
    School of Pharmacy, West Virginia University, Morgantown, WV, USA
    Pharmacol Ther 127:271-82. 2010
    ..Among them, current data suggests that sigma receptors are involved in multiple processes effecting antidepressant-like actions in vivo and in vitro...
  40. pmc Sigma receptors suppress multiple aspects of microglial activation
    Aaron A Hall
    Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida 33612 4799, USA
    Glia 57:744-54. 2009
    ..Microglia express high levels of sigma receptors, however, the function of these receptors in microglia and how they may affect the activation of these cells ..
  41. ncbi Substance P(1-7) induces antihyperalgesia in diabetic mice through a mechanism involving the naloxone-sensitive sigma receptors
    Anna Carlsson
    Department of Pharmaceutical Biosciences, Uppsala University, P O Box 591, S 751 24 Uppsala, Sweden
    Eur J Pharmacol 626:250-5. 2010
    ..These results suggest that hyperalgesia in diabetic mice may be, in part, due to the enhanced endogenous sigma(1) receptor systems in the spinal cord...
  42. ncbi Neurosteroids and sigma1 receptors, biochemical and behavioral relevance
    T Maurice
    Laboratory of Cerebral Plasticity, CNRS FRE 2693, University of Montpellier II, CC 090, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France
    Pharmacopsychiatry 37:S171-82. 2004
    ....
  43. ncbi High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503
    Masatomo Ishikawa
    Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
    Biol Psychiatry 62:878-83. 2007
    ..The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain...
  44. ncbi Preserved sigma1 (sigma1) receptor expression and behavioral efficacy in the aged C57BL/6 mouse
    Vân Ly Phan
    Behavioral Neuropharmacology Group, INSERM U 336, Institut de Biologie, 4, bvd Henri IV, 34060 Montpellier, France
    Neurobiol Aging 24:865-81. 2003
    ..Targeting this unique receptor may offer an original drug strategy during aging...
  45. ncbi Behavioral effects of rimcazole analogues alone and in combination with cocaine
    Jonathan L Katz
    Department of Health and Human Services, Medications Discovery Research Branch, NIDA Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
    Eur J Pharmacol 468:109-19. 2003
    ..effects of cocaine, and though the mechanism for these effects is not presently clear, it is possible that this attenuation maybe mediated by actions of the rimcazole analogues at the dopamine transporter and/or sigma receptors.
  46. ncbi Stimulation of rat striatal tyrosine hydroxylase activity following intranigral administration of sigma receptor ligands
    S D Weiser
    Department of Psychology, Schrier Research Laboratory, Brown University, Providence, RI, USA
    Eur J Pharmacol 275:1-7. 1995
    ..These results indicate that occupancy of sigma receptors in the substantia nigra is associated with an activation of dopamine formation in dopaminergic terminals in ..
  47. ncbi Electrophysiological effects of selective sigma-receptor agonists, antagonists, and the selective phencyclidine receptor agonist MK-801 on midbrain dopamine neurons
    G F Steinfels
    E I du Pont de Nemours and Co, Inc, Medical Products Department, Wilmington, Delaware 19880 0400
    Neuropsychopharmacology 2:201-8. 1989
    ..However, the relative potencies do not correspond to their relative binding affinities, suggesting that non-PCP-receptor properties may mediate this effect...
  48. ncbi Sigma receptors: potential medications development target for anti-cocaine agents
    Rae R Matsumoto
    Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, P O Box 26901, CPB 337, Oklahoma City, OK 73190, USA
    Eur J Pharmacol 469:1-12. 2003
    The ability of cocaine to interact with sigma receptors suggests a viable target for medications development...
  49. ncbi Sigma receptors: recent advances and new clinical potentials
    W D Bowen
    Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0815, USA
    Pharm Acta Helv 74:211-8. 2000
    Several recent advances are leading to a better understanding of sigma receptors. Here we focus on our recent findings regarding cellular functions of sigma-2 receptors and discuss their possible clinical implications...
  50. ncbi (+)-6,7-benzomorphan sigma ligands stimulate dopamine synthesis in rat corpus striatum tissue
    R G Booth
    Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599
    Brain Res 557:349-52. 1991
    ..These results suggest that these (+)-benzomorphans may act as agonists at putative sigma heteroreceptors on striatal nerve terminals, or through an indirect mechanism, to modulate dopamine synthesis...
  51. ncbi Functional polymorphisms in the sigma1 receptor gene associated with alcoholism
    Ryosuke Miyatake
    Institute of Clinical Research, National Alcoholism Center Kurihama Hospital, Kanagawa, Japan
    Biol Psychiatry 55:85-90. 2004
    ..To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study...
  52. ncbi Sigma receptors modulate both A9 and A10 dopaminergic neurons in the rat brain: functional interaction with NMDA receptors
    S Iyengar
    Searle Research and Development, G D Searle and Co, St Louis, MO 63198
    Brain Res 524:322-6. 1990
    ..b>Sigma receptors thus appear to modulate dopaminergic function in both A9 and A10 projections...
  53. ncbi Involvement of the sigma1 receptor in the appetitive effects of cocaine
    T Maurice
    Laboratory of Cerebral Plasticity, CNRS FRE 2693, University of Montpellier II, CC 090, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France
    Pharmacopsychiatry 37:S198-207. 2004
    ..The physiological interaction between cocaine and sigma (1) receptors is detailed and the possibility that effective therapeutical strategies could target the sigma (1) receptor is considered...
  54. ncbi Intracellular dynamics of sigma-1 receptors (sigma(1) binding sites) in NG108-15 cells
    Teruo Hayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA
    J Pharmacol Exp Ther 306:726-33. 2003
    ....
  55. ncbi Protein kinase C-dependent potentiation of intracellular calcium influx by sigma1 receptor agonists in rat hippocampal neurons
    F P Monnet
    Hôpital Charcot, and Institut National de la Santé et de la Recherche Médicale INSERM Unité 488, 80 rue du General Leclerc, F 94276 Kremlin Bicêtre cedex, France
    J Pharmacol Exp Ther 307:705-12. 2003
    ..Our results provide further support for a general mechanism for the intracellular sigma1 receptor to regulate Ca2+-dependent signal transduction and protein phosphorylation...
  56. ncbi Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine
    Magali Peeters
    Laboratoire de Pharmacologie Expérimentale FARL, Universite Catholique de Louvain, 54 10, Avenue Hippocrate 54, B 1200 Brussels, Belgium
    Eur J Neurosci 19:2212-20. 2004
    ..Together, these data demonstrate that aminoadamantanes behave as sigma1 receptor agonists, and confirm an involvement of this receptor in modulating dopamine receptors exerted by therapeutically relevant concentrations of amantadine...
  57. ncbi Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system
    G Alonso
    INSERM Unité 336, Developpement, Plasticite et Vieillissement du Systeme Nerveux, Montpellier, France
    Neuroscience 97:155-70. 2000
    ..These data indicate that the sigma(1) receptor antibody prepared here, represents a promising tool for further investigating the role of sigma(1) receptors...
  58. ncbi Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress
    Marie Stampe Ostenfeld
    Apoptosis Department, Institute for Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Cancer Res 65:8975-83. 2005
    ..c. fibrosarcoma models in mice. These results present siramesine as a promising new drug for the treatment of tumors resistant to traditional therapies...
  59. ncbi Characterization of the cocaine binding site on the sigma-1 receptor
    Yuenmu Chen
    Department of Pharmacology, University of Wisconsin Madison School of Medicine and Public Health, 1300 University Avenue, Madison, Wisconsin 53706 1532, USA
    Biochemistry 46:3532-42. 2007
    ..Systematic truncation of the C-terminus indicated the requirement for the last 15 amino acid residues of the receptor for [125I]IACoc photolabeling...
  60. ncbi Function of sigma1 receptors in Parkinson's disease
    M Mishina
    The Department of Neurology, Neurological Institute, Nippon Medical School Chiba Hokusoh Hospital, Inba gun, Chiba, Japan
    Acta Neurol Scand 112:103-7. 2005
    ....
  61. ncbi Sigma1 receptor upregulation after chronic methamphetamine self-administration in rats: a study with yoked controls
    Roman Stefanski
    Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, NIDA IRP, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    Psychopharmacology (Berl) 175:68-75. 2004
    ..Involvement of Sig-1R in the self-administration of psychostimulants, however, has never been reported...
  62. ncbi Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent
    S R Choi
    Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nucl Med Biol 28:657-66. 2001
    ..This is the first time a subtype-selective 99mTc-labeled agent for imaging sigma receptor sites is reported...
  63. ncbi Small molecule antagonists of the sigma-1 receptor cause selective release of the death program in tumor and self-reliant cells and inhibit tumor growth in vitro and in vivo
    Barbara A Spruce
    Department of Surgery and Molecular Oncology, The University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Cancer Res 64:4875-86. 2004
    ..Release of a sigma receptor-mediated brake on apoptosis may offer a new approach to cancer treatment...
  64. pmc Differential involvement of the sigma(1) (sigma(1)) receptor in the anti-amnesic effect of neuroactive steroids, as demonstrated using an in vivo antisense strategy in the mouse
    T Maurice
    INSERM U 336, Behavioural Neuropharmacology Group, Institut de Biologie, 4, blvd Henri IV, 34060 Montpellier, France
    Br J Pharmacol 134:1731-41. 2001
    ..5. These observations bring a molecular basis to the modulatory role of sigma(1) receptors in memory, and reveal that the anti-amnesic action of neuroactive steroids may not similarly involve an interaction with sigma(1) receptors...
  65. ncbi Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also via sigma receptors
    Shinichi Nakao
    Department of Anesthesiology, Kansai Medical University, 10 15 Fumizono cho, Moriguchi Shi, Osaka, Japan
    Brain Res 926:191-6. 2002
    ..We investigated whether NMDA and/or sigma receptors were involved in the c-Fos expression...
  66. ncbi Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines
    Keith W Crawford
    Howard University College of Medicine, Department of Pharmacology, Washington, DC 20059, USA
    Cancer Res 62:313-22. 2002
    ..These observations further suggest that sigma-2 receptors may be targets that can be therapeutically exploited in the treatment of both drug-sensitive and drug-resistant metastatic tumors...
  67. ncbi Synthesis and evaluation of 11C- and 18F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies
    Kazunori Kawamura
    Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    Nucl Med Biol 30:273-84. 2003
    ..All radioligands showed the receptor-specific binding in the brain, and visualized similar regional brain distributions by ex vivo autoradiography. The [(11)C]ethoxy analogs were relatively labile for metabolism...
  68. ncbi Sigma1 receptor ligands and related neuroactive steroids interfere with the cocaine-induced state of memory
    Pascal Romieu
    Behavioral Neuropharmacology Group, INSERM U 336, Institut de Biologie, Montpellier, France
    Neuropsychopharmacology 31:1431-43. 2006
    ....
  69. ncbi The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities
    T Maurice
    Behavioural Neuropharmacology Group, INSERM U 336, Institut de Biologie, 4 Bvd HENRI IV, 34060, Montpellier, France
    Brain Res Brain Res Rev 37:116-32. 2001
    ..The therapeutical interest of selective sigma1 receptor agonists in alleviating aging-related cognitive deficits will be discussed...
  70. ncbi Neurosteroid enhances glutamate release in rat prelimbic cortex via activation of alpha1-adrenergic and sigma1 receptors
    Y Dong
    State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, Shanghai, 200032, People s Republic of China
    Cell Mol Life Sci 62:1003-14. 2005
    ..Intracellular calcium, protein kinase C and adenylyl cyclase might be upstream events in the activation of protein kinase A after PREGS...
  71. ncbi Sigma1 receptor modulation of opioid analgesia in the mouse
    Jianfeng Mei
    The Laboratory of Molecular Neuropharmacology, Memorial Sloan Kettering Cancer Center, Program in Neurosciences, Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    J Pharmacol Exp Ther 300:1070-4. 2002
    ..This enhanced response following antisense treatment was similar to that seen with haloperidol. These observations confirm the importance of sigma1 receptors as a modulatory system influencing the analgesic activity of opioid drugs...
  72. ncbi Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: implications for antidepressants
    Minoru Takebayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Pharmacol Exp Ther 303:1227-37. 2002
    ..Thus, when taken together, our results indicate that Sig-1R play an important role in the NGF-induced neurite sprouting and that certain antidepressants may facilitate neuronal sprouting in the brain via Sig-1R...
  73. ncbi Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma 1 receptors of guinea pig brain
    Enrique J Cobos
    Department of Pharmacology and Institute of Neuroscience, School of Medicine, University of Granada, 18012 Granada, Spain
    Synapse 55:192-5. 2005
    ..Therefore, determining in vitro the differential modulation by DPH of sigma(1) ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different sigma(1) ligands...
  74. ncbi Sigma receptors and sigma ligands: background to a pharmacological enigma
    B E Leonard
    Pharmacology Department, National University of Ireland, Galway, Ireland
    Pharmacopsychiatry 37:S166-70. 2004
    Although it is now well established that the sigma receptors are distinct from neurotransmitter, neuropeptide and steroid receptors, their precise physiological role, and possible involvement in the pathology of neurological and ..
  75. ncbi The role of sigma receptors in depression
    Jordanna E Bermack
    Department of Psychiatry, McGill University, Montreal, Quebec, Canada
    J Pharmacol Sci 97:317-36. 2005
    Behavioral models used to test potential antidepressants have shown that ligands that bind to sigma receptors possess "antidepressant-like" properties...
  76. ncbi Involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy
    Masayuki Hiramatsu
    Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Meijo University, Tenpaku ku, Nagoya 468 8503, Japan
    Brain Res 1030:247-55. 2004
    ..Furthermore, kappa-opioid receptors agonist showing analgesic effects act on kappa-opioid receptors or sigma receptors and play important roles only when memory function is impaired, but the two neuronal systems regulate memory ..
  77. ncbi Lu 28-179 labels a sigma(2)-site in rat and human brain
    Karina Krøyer Søby
    Department of Molecular Pharmacology, H Lundbeck A S, Biological Research, DK 2500, Valby, Denmark
    Neuropharmacology 43:95-100. 2002
    ..Overall, these data are consistent with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site...
  78. ncbi Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells
    Enrique J Cobos
    Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine, University of Granada, Granada, Spain
    J Neurochem 102:812-25. 2007
    ..These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP...
  79. ncbi The antidepressant-like effect induced by the sigma(1) (sigma(1)) receptor agonist igmesine involves modulation of intracellular calcium mobilization
    Alexandre Urani
    Département de Biochimie Enzymologie, Pfizer GRD Fresnes, 3 9, rue de la Loge, BP 100, 94265 Fresnes Cedex, France
    Psychopharmacology (Berl) 163:26-35. 2002
    ..At the behavioral level, sigma(1) agonists modulate learning, response to stress and depression. In particular, the selective sigma(1) agonist igmesine reduced immobility in the forced swimming test...
  80. ncbi Formalin-induced pain is reduced in sigma(1) receptor knockout mice
    Cruz Miguel Cendan
    Department of Pharmacology and Institute of Neurosciences, School of Medicine, University of Granada, Avenida de Madrid 12, 18012 Granada, Spain
    Eur J Pharmacol 511:73-4. 2005
    ..These results suggest that the tonic pain induced by formalin is altered in mice lacking sigma1 receptors, and highlight the potential usefulness of further studies of the role of sigma1 receptors in models of non-acute pain...
  81. ncbi Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study
    Aren van Waarde
    PET Center, Groningen University Hospital, 9700 RB Groningen, The Netherlands
    J Nucl Med 45:1939-45. 2004
    ..Our objective was to study 2 radioligands for visualization of sigma-receptors with PET...
  82. ncbi Distinct modulatory roles of sigma receptor subtypes on glutamatergic responses in the dorsal hippocampus
    Jordanna E Bermack
    Department of Psychiatry, McGill University, Montreal, Quebec, Canada H3A 1A1
    Synapse 55:37-44. 2005
    ..Thus, this study set out to characterize 4-IBP's action at sigma receptors using the hippocampal paradigm of sigma ligand activity...
  83. ncbi Sigma receptor antagonists inhibit human lens cell growth and induce pigmentation
    Lixin Wang
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
    Invest Ophthalmol Vis Sci 46:1403-8. 2005
    ..The expression of the Sigma 1 receptor and the ability of receptor antagonists to inhibit growth and induce pigment formation were investigated in human lens epithelial cells...
  84. ncbi Antiproliferative and cytotoxic effects of some sigma2 agonists and sigma1 antagonists in tumour cell lines
    Nicola Antonio Colabufo
    Dipartimento Farmaco Chimico, via Orabona, 4, 70126 Bari, Italy
    Naunyn Schmiedebergs Arch Pharmacol 370:106-13. 2004
    ....
  85. ncbi Sigma receptors: from discovery to highlights of their implications in the cardiovascular system
    Laurent Monassier
    Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculte de Medecine, 11 rue Humann, 67085 Strasbourg Cedex, France
    Fundam Clin Pharmacol 16:1-8. 2002
    b>Sigma receptors are the targets of many ligands, of which some (the haloperidol for instance) are psychoactive, and of substances known to have antiarrhythmic effects (amiodarone and clofilium)...
  86. ncbi A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors
    M Takebayashi
    Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    Pharmacopsychiatry 37:S208-13. 2004
    b>Sigma receptors were first described as one of the opiate receptor subtypes...
  87. ncbi Metabotropic neurosteroid/sigma-receptor involved in stimulation of nociceptor endings of mice
    H Ueda
    Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Nagasaki, Japan
    J Pharmacol Exp Ther 298:703-10. 2001
    ....
  88. ncbi Neuroprotective effect of sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) is linked to reduced neuronal nitric oxide production
    T Goyagi
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Stroke 32:1613-20. 2001
    ..Neuroprotective effects of PPBP are lost when nNOS is not present or is inhibited; therefore, PPBP likely acts upstream from NO generation and its subsequent neurotoxicity...
  89. ncbi In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as measured with the positron emission tomography radioligand [18F]FPS
    Rikki N Waterhouse
    Department of Psychiatry, Columbia University, New York, New York, USA
    Synapse 61:540-6. 2007
    ....
  90. ncbi SA4503, a novel cognitive enhancer with sigma1 receptor agonist properties, facilitates NMDA receptor-dependent learning in mice
    T Maurice
    Unité 336 de l Institut National de la Santé et de la Recherche Médicale, Developpement, Plasticite et Vieillissement du Systeme Nerveux, E N S C M, Montpellier, France
    Eur J Pharmacol 328:9-18. 1997
    ..Pertinent informations on the potential mechanism of the anti-amnesic effects of sigma1 receptor ligands were also obtained...
  91. pmc The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus
    Marzia Martina
    Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada
    J Physiol 578:143-57. 2007
    ..Therefore, the block of SK channels and the resulting increased Ca2+ influx through the NMDAR enhances NMDAR responses and LTP. These results emphasize the importance of the sigmaR-1 as postsynaptic regulator of synaptic transmission...
  92. ncbi Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to sigma 1 receptors in the mouse forebrain
    T Maurice
    INSERM U 336, Ecole Nationale Superieure de Chimie, Montpellier, France
    J Neurosci Res 46:734-43. 1996
    ....
  93. ncbi A feasibility study of [11C]SA4503-PET for evaluating sigmal receptor occupancy by neuroleptics: the binding of haloperidol to sigma1 and dopamine D2-like receptors
    Kiichi Ishiwata
    Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan
    Ann Nucl Med 20:569-73. 2006
    ..We concluded that [11C]SA4503-PET can be used for evaluating the sigma1R occupancy rates by neuroleptics or other drugs...
  94. ncbi Mapping of human cerebral sigma1 receptors using positron emission tomography and [11C]SA4503
    Muneyuki Sakata
    Graduate School of Information Science, Nara Institute of Science and Technology, Japan
    Neuroimage 35:1-8. 2007
    ..We concluded that this method enables the quantitative analysis of sigma1Rs in the human brain...
  95. ncbi A new sigma ligand, (+/-)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect
    Orazio Prezzavento
    Department of Pharmaceutical Sciences, University of Catania, Viale A Doria, 6, 95125 Catania, Italy
    Life Sci 82:549-53. 2008
    ..This study confirms that (+/-)-PPCC plays the role of sigma agonist in this model and strengthens the hypothesis of the sigma receptor modulatory role on KOP-mediated analgesia...
  96. ncbi Imaging sigma receptors: applications in drug development
    Thomas Lee Collier
    Siemens Biomarker Solutions, 406 Industrial Drive, North Wales, PA 19454, USA
    Curr Pharm Des 13:51-72. 2007
    b>Sigma receptors have been implicated in a myriad of cellular functions, biological processes and diseases...
  97. ncbi Subcellular localization of sigma-2 receptors in breast cancer cells using two-photon and confocal microscopy
    Chenbo Zeng
    Department of Radiology, Division of Radiological Sciences, Washington University School of Medicine, 510 S Kingshighway Boulevard, St Louis, MO 63110, USA
    Cancer Res 67:6708-16. 2007
    ....
  98. ncbi Rapid reduction of sigma1-receptor binding and 18F-FDG uptake in rat gliomas after in vivo treatment with doxorubicin
    Aren van Waarde
    Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Nucl Med 48:1320-6. 2007
    ....
  99. ncbi sigma(2)-receptor ligand-mediated inhibition of inwardly rectifying K(+) channels in the heart
    Laurent Monassier
    Laboratoire de Neurobiologie et de Pharmacologie Cardiovasculaire, Facultéde Médecine, INSERM U 715, 11 rue Humann, 67085 Strasbourg, France
    J Pharmacol Exp Ther 322:341-50. 2007
    ..The repolarization prolongation and the early-afterdepolarization can be responsible for "torsades de pointe" and sudden cardiac death...
  100. ncbi Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3alpha-yl carbamate analogs as sigma2 receptor ligands
    Suwanna Vangveravong
    Division of Radiological Sciences, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St Louis, MO 63110, USA
    Bioorg Med Chem 14:6988-97. 2006
    ..These compounds were also used in the preparation of biotinylated and fluorescent probes of the sigma(2) receptor...
  101. ncbi The sigma-2 receptor agonist PB28 inhibits calcium release from the endoplasmic reticulum of SK-N-SH neuroblastoma cells
    Giuseppe Cassano
    Dipartimento di Fisiologia Generale ed Ambientale, Universita di Bari, Via Amendola 165 A, 70126 Bari, Italy
    Cell Calcium 40:23-8. 2006
    ..b>Sigma receptors are divided into the subtypes sigma-1 and sigma-2, which are expressed in tumor cell lines and characterized ..

Research Grants62

  1. Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.
    Sylvia B Smith; Fiscal Year: 2013
    ..The proposed project will extend these findings to understand the mechanism of this protection with the ultimate goal of determining whether (+)- pentazocine may be useful clinically for retinopathy in humans. ..
  2. Effect of chronic antipsychotic medication administration on cocaine poisoning
    KENNON JAMES HEARD; Fiscal Year: 2010
    ..5-HT2C and 5-HT3 serotonin;a1- and a2-adrenergic;NMDA and AMPA glutamate;GABAA;muscarinic cholinergic;and sigma receptors and of monoamine transporters...
  3. LPD Nanoparticles in Anti-Cancer Therapy
    Leaf Huang; Fiscal Year: 2012
    ..A self-assembled nanoparticle formulation will be used as a delivery vehicle. The project uses lung cancer and lung metastasis in mice as the disease model. ..
  4. Center of Research Excellence in Natural Products Neuroscience (CORE-NPN)
    STEPHEN JOHN CUTLER; Fiscal Year: 2013
    ..abstract_text> ..
  5. DEVELOPMENT OF VESICULAR ACETYLCHOLINE TRANSPORTER IMAGING AGENTS FOR PET
    Zhude Tu; Fiscal Year: 2010
    ..Therefore, a radiotracer that possesses a high affinity and high selectivity for VAChT versus sigma receptors and good pharmacokinetic characteristics would be of tremendous use to the PET community...
  6. Molecular Mechanisms of Sigma Receptor 1-Mediated Neuroprotection
    Kathryn Bollinger; Fiscal Year: 2013
    ..abstract_text> ..
  7. Contribution of Sigma Receptor Activation to Neuropathic Pain
    Hsiang En Wu; Fiscal Year: 2013
    ..settings that will expand independence as a scientist;3) apply this new knowledge to examine the role of sigma receptors (aR) in traumatic painful neuropathy and inflammatory pain...
  8. Development of Anti-Cocaine Medications
    JOHN RILEY LEVER; Fiscal Year: 2010
    ..We are proposing laboratory studies of compounds that target special proteins, called sigma receptors, that are involved in cocaine's addictive power...
  9. GENDER AND SEX HORMONES AND OPIOID ANALGESIA
    Jon Levine; Fiscal Year: 2006
    ..These studies will provide much-needed knowledge of gender differences in responses to opioid analgesics and should lead to gender- specific recommendations for more effective, better targeted pain therapy. ..
  10. Proteomic Characterization of the Sigma-1 Receptor and Its Signaling Complex
    Carthene R Bazemore Walker; Fiscal Year: 2010
    ..This is important because the sigma receptors represent a novel class of proteins that when activated by psychostimulants, such as cocaine and ..
  11. Immune Tolerance; Sigma Receptor as a Therapeutic Target
    Vadivel Ganapathy; Fiscal Year: 2003
    ....
  12. SIGMA LIGAND ELECTROPHYSIOLOGY IN RAT HIPPOCAMPAL SLICE
    Christine Eccles; Fiscal Year: 1991
    b>Sigma receptors were defined originally in terms of opiate responses and later became associated with the phencyclidine (PCP) receptor. PCP's psychotomimetic effects suggested a possible role of sigma receptors in psychiatric processes...
  13. NOVEL SIGMA RECEPTOR LIGANDS IN NEURODEGENERATION
    Raymond Booth; Fiscal Year: 2000
    ....
  14. O-RECEPTOR PSYCHOTOMIMETICS: ACTIONS ON SINGLE NEURONS
    John Williams; Fiscal Year: 1992
    ..Equally important, the results may lead to a better understanding of the pathogenesis of and new therapies for schizophrenia...
  15. Sigma Receptor Structure /Function /K+ Channel Modulation
    ARNOLD RUOHO; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Sigma receptors are unique "non-opioid" receptors that are found in the mammalian central nervous system and peripheral organs...
  16. SIGMA RECEPTORS & PSYCHOTOMIMETIC DRUG ACTION
    Charles Chavkin; Fiscal Year: 1993
    ..results which suggested that an endogenous sigma transmitter is released from nerve terminals to bind to sigma receptors in the rat hippocampus...
  17. MOLECULAR MECHANISMS OF PCP AND SIGMA DRUG ACTION
    LINDA WERLING; Fiscal Year: 2001
    ..nucleus accumbens, prefrontal cortex, hippocampus and cerebellum, we have shown that one role of the sigma receptors is regulation of catecholamine release...
  18. STUDIES ON SIGMA RECEPTORS AND THEIR LIGANDS
    Eckard Weber; Fiscal Year: 1993
    DESCRIPTION (Adapted from the Applicant's Abstract): Sigma receptors are high affinity binding sites for haloperidol and other antipsychotic drugs...
  19. EVALUATION OF PCP AND SIGMA EFFECTS ON DA PHYSIOLOGY
    Arthur Freeman; Fiscal Year: 1992
    ..at a site designated the "PCP receptor," and also interacts with haloperidol-sensitive sigma binding sites ("sigma receptors")...
  20. PROGESTERONE AFTER TRAUMATIC BRAIN INJURY
    Donald Stein; Fiscal Year: 2005
    ..an in vitro model of injury, progesterone's short-term neuroprotective effects are mediated specifically via sigma receptors; (3) if progesterone will prevent loss of mitochondrial function by reducing oxidative stress initiated in ..
  21. MEMBRANE EXCITABILITY AND SECRETION FROM NERVE ENDINGS
    Meyer Jackson; Fiscal Year: 2007
    ..Experiments will explore how NO and the NO signaling cascade modulate ion channels. The second involves sigma receptors, which modulate posterior pituitary ion channels in response to a number of ligands, including antipsychotic ..
  22. Reversing the toxic effects of drugs of abuse
    Andrew Coop; Fiscal Year: 2009
    ..This award will allow the candidate to be relieved from many teaching and administrative responsibilities, thereby allowing him to focus on current and future research projects. ..
  23. SIGMA RECEPTOR SPECIFIC RADIOPHARM FOR IMAGING TUMORS
    Christy John; Fiscal Year: 1999
    ..The applicants reported having recently characterized the expression of a high density of sigma receptors on MCF-7 (adenocarcionma), T47D (ductal), and MDA MB231 (adenocarcinoma) breast tumor cells and human ..
  24. ROLE OF SIGMA RECEPTORS IN MOVEMENT DISORDERS
    Wayne Bowen; Fiscal Year: 1991
    b>Sigma receptors are non-dopaminergic, non-opioid receptors which bind several neuroleptic drugs and the (+)-enantiomer of some opiate benzomorphans...
  25. The Delayed Effects of Phencyclidine: Mechanisms
    Sarah Turgeon; Fiscal Year: 2002
    ..Because both sigma receptors and the medial prefrontal cortex have been implicated in the pathophysiology of schizophrenia, PCP's actions ..
  26. Expanding the therapeutic window for stroke treatment.
    KEITH PENNYPACKER; Fiscal Year: 2009
    ..We have found that activation of sigma receptors decrease infarct area by over 80% when delivered 24 hours post- stroke in the rat...
  27. COCAINE SMOKING EFFECTS ON LUNG IMMUNITY & HOST DEFENSE
    Michael Roth; Fiscal Year: 2006
    ..Novel experiments have identified sigma receptors as likely to be involved in these effects both in vitro and in vivo...
  28. DITOLYL GUANIDINE ANALOGS AS ANTIPSYCHOTIC DRUGS
    James Fischer; Fiscal Year: 1991
    ..At the same time we will initiate the development steps necessary to obtain an IND. These will include bulk chemical synthesis, development of a chemical assay, pharmacology safety and metabolism studies and full-scale toxicity testing...
  29. Structural and Functional Analysis of the Sigma-1 Receptor
    Wolfgang Peti; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Sigma receptors are a biologically important family of integral membrane receptors that are critical for learning, memory, drug addiction and aging diseases such as Alzheimer's disease...
  30. Cocaine, Sigma Receptors and Fra-2
    Rae Matsumoto; Fiscal Year: 2006
    ..studies conclusively demonstrate that pharmacological antagonists or antisense oligonucleotides targeting sigma receptors prevent the convulsive, lethal, locomotor stimulant, and rewarding properties of cocaine in mice...
  31. Characterization of the Sigma-1 Receptor
    DOMINIQUE FONTANILLA; Fiscal Year: 2009
    ..Elucidating the structure of the sigma-1 receptor and it's binding site will provide insight as to the functional role of the sigma-1 receptor as well as it's potential as a drug target. ..
  32. Presynaptic Site of Action of Neurosteroids
    L Partridge; Fiscal Year: 2003
    ..Specifically we will test a role of sigma receptors, voltage-gated calcium channels and potassium channels...
  33. VULNERABILITY TO COCAINE TOXICITY--GENETIC MECHANISMS
    MARY RITZ; Fiscal Year: 1999
    ..These CNS receptors include serotonin transporters and serotonergic 5HT1, 5HT2, 5HT3, muscarinic M1, and sigma receptors. Another objective of this study is assessment of the effectiveness of specific pharmacological interventions ..
  34. ISOLATION & CHARACTERIZATION OF THE SIGMA-RECEPTOR
    RANDALL MURPHY; Fiscal Year: 1992
    ..The relationship of the putative SRBS subtypes will be clarified through pharmacological studies of the affinity-purified SRBS and the expressed SRBS gene product using a variety of radioligands...
  35. SELECTIVE SIGMA LIGANDS: DESIGN SYNTHESIS & EVALUATION
    RICHARD GLENNON; Fiscal Year: 1993
    ..In addition, on the basis of our preliminary results, we also propose to prepare new radioligands that should be useful for the further characterization of sigma receptor/binding sites...
  36. MECHANISMS OF REGULATION OF CEREBRAL BLOOD FLOW
    Patricia Hurn; Fiscal Year: 2007
    ..This program is supported by 3 Core facilities: 1) Administration; 2) Cells and Tissues-Culture and Neuropathology; and 3) Transgenic Animals. ..
  37. SIGMA LIGANDS:PROTECTION OF DIABETES-INDUCED RETINOPATHY
    Sylvia Smith; Fiscal Year: 2001
    ..Finally in AIM 3, the investigator will use various methods to confirm the presence of type 1 sigma ligand in the retina. The investigator will analyze the pattern of type 1 sigma receptor expression in the retina. ..
  38. NOVEL CEREBROPROTECTIVE AGENTS
    MICHAEL PONTECORVO; Fiscal Year: 1990
    ....
  39. Vascular and Metabolic Mechanisms in Alzheimer's Disease
    Robert Mach; Fiscal Year: 2009
    ..Through the use of the unique resources and personnel at Washington University Medical Center, we have the opportunity to provide answers to important clinical and mechanistic questions in AD. ..
  40. DEVELOPMENT OF D3 ANTAGONISTS TO TREAT COCAINE ADDICTION
    Robert Mach; Fiscal Year: 2002
    ..In addition, this research will result in the development of radiolabeled probes for studying both the function of D3 receptors in the CNS and the alteration in D3 receptor density thatoccurs as a consequence of cocaine abuse. ..
  41. Dopamine D3 Receptor Imaging Agents for PET and SPECT
    Robert Mach; Fiscal Year: 2006
    ..A secondary goal of this project is to develop an iodine-125 labeled radiotracer for in vitro binding studies of the D3 receptor. ..
  42. PET Imaging of Breast Cancer via Sigma-2 Receptors
    Robert Mach; Fiscal Year: 2006
    ..abstract_text> ..
  43. PET Radiotracers for Imaging Apoptosis
    Robert Mach; Fiscal Year: 2004
    ..If successful, the research described in this research proposal will provide a PET-based imaging procedure for measuring apoptosis that will be of tremendous value to the PET research community. ..
  44. Radiolabeled Probes for Imaging Caspase 3 Activation
    Robert Mach; Fiscal Year: 2008
    ..abstract_text> ..
  45. Dopamine D2 Selective Imaging Agents
    Robert Mach; Fiscal Year: 2008
    ..A secondary goal of this project is to develop an iodine-125 labeled radiotracer for in vitro binding studies of the D2 receptor. ..
  46. SIGMA LIGANDS FOR THE TREATMENT OF COCAINE OVERDOSE
    Rae Matsumoto; Fiscal Year: 2007
    ..These compounds, as well as antisense oligodeoxynucleotides against sigma receptors, also attenuate cocaine-induced locomotor activity, suggesting that they can block both the behavioral toxic ..
  47. Synthesis and Evaluation of Sigma-Active Cocaine Antagonists
    Rae R Matsumoto; Fiscal Year: 2010
    ..It is anticipated that the results of this project will stimulate the rational development of new a2 receptor probes and ultimately contribute to improved treatments for psychostimulant abuse. ..
  48. Role of sigma receptors in ethanol reinforcement
    Valentina Sabino; Fiscal Year: 2008
    ..to be conducted at The Scripps Research Institute in the rich neuroscience community of San Diego, concerns sigma receptors, unique mammalian binding sites that modulate other neurotransmitter systems and which are richly expressed ..
  49. Development of PET Radioligands for NMDA Receptors
    Rikki Waterhouse; Fiscal Year: 2004
    ..The data obtained will be pivotal for the design of studies to non-invasively assess NMDA receptor function and will identify suitable radiotracers and provide preliminary data to support future grant submissions. ..
  50. NEUROLEPTIC SPACER LENGTH GOVERNS MOLECULAR RECOGNITION
    John Schetz; Fiscal Year: 2009
    ....
  51. Ethanol-Neurosteroid Actions on Synaptic Transmission
    Jilla Sabeti; Fiscal Year: 2006
    ..Collectively, the experiments will advance our understanding of changes in neurosteroid modulation of synaptic function that may be important to the CNS actions of ethanol. ..
  52. ESTROGEN EFFECTS ON DOPAMINE AUTORECEPTOR ACTIVITY
    Tina Thompson; Fiscal Year: 2003
    ....
  53. Pharmacotherapy for Minor Depression
    Robert Howland; Fiscal Year: 2004
    ..The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. ..
  54. Neurodevelopmental Apoptosis
    Nuri Farber; Fiscal Year: 2008
    ..abstract_text> ..