Gene Symbol: Sigmar1
Description: sigma non-opioid intracellular receptor 1
Alias: Oprs1, sigma non-opioid intracellular receptor 1, opioid receptor, sigma 1, sigma 1-type opioid receptor, sigma1-receptor, sigma1R
Species: rat
Products:     Sigmar1

Top Publications

  1. Takebayashi M, Hayashi T, SU T. Sigma-1 receptors potentiate epidermal growth factor signaling towards neuritogenesis in PC12 cells: potential relation to lipid raft reconstitution. Synapse. 2004;53:90-103 pubmed
    ..sigma-1R may thus play an important role in directing EGF signaling towards neuritogenesis, perhaps by shifting EGFR from the lipid raft into non-raft regions. ..
  2. Hayashi T, Su T. Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc Natl Acad Sci U S A. 2001;98:491-6 pubmed
  3. Hayashi T, SU T. Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation. Proc Natl Acad Sci U S A. 2004;101:14949-54 pubmed
    ..Our findings indicate that, in the brain, Sig-1Rs targeting GalCer-containing lipid microdomains are important for OL differentiation and that Sig-1Rs may play an important role in the pathogenesis of certain demyelinating diseases. ..
  4. Mei J, Pasternak G. Sigma1 receptor modulation of opioid analgesia in the mouse. J Pharmacol Exp Ther. 2002;300:1070-4 pubmed
    Opioid analgesia is influenced by many factors, including the sigma1 receptor system. Current studies show the importance of supraspinal mechanisms in these sigma1actions...
  5. Seth P, Fei Y, Li H, Huang W, Leibach F, Ganapathy V. Cloning and functional characterization of a sigma receptor from rat brain. J Neurochem. 1998;70:922-31 pubmed
    ..Northern blot analysis with poly(A)+ RNA isolated from various rat tissues has indicated that the sigma receptor-specific transcript, 1.6 kb in size, is expressed abundantly in liver and moderately in intestine, kidney, brain, and lung. ..
  6. Tchedre K, Huang R, Dibas A, Krishnamoorthy R, Dillon G, Yorio T. Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction. Invest Ophthalmol Vis Sci. 2008;49:4993-5002 pubmed publisher
    ..Regulation of calcium influx in RGCs by sigma-1 receptor ligands may represent in part the neuroprotective effect of sigma-1 receptors. ..
  7. Takebayashi M, Hayashi T, SU T. Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: implications for antidepressants. J Pharmacol Exp Ther. 2002;303:1227-37 pubmed
    ..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. ..
  8. Mei J, Pasternak G. Molecular cloning and pharmacological characterization of the rat sigma1 receptor. Biochem Pharmacol. 2001;62:349-55 pubmed
    In an effort to further understand the pharmacology of sigma receptors, we have cloned the rat homolog of the sigma1 receptor. We isolated a cDNA clone (rs2-2) from rat brain tissue using reverse transcriptase-polymerase chain reaction (..
  9. Alonso G, Phan V, Guillemain I, Saunier M, Legrand A, Anoal M, et al. Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system. Neuroscience. 2000;97:155-70 pubmed
    ..These data indicate that the sigma(1) receptor antibody prepared here, represents a promising tool for further investigating the role of sigma(1) receptors. ..

More Information


  1. Aydar E, Palmer C, Klyachko V, Jackson M. The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron. 2002;34:399-410 pubmed
    ..The ligand-independent effects on channels suggest that sigma receptors serve as auxiliary subunits to voltage-gated K+ channels with distinct functional interactions, depending on the presence or absence of ligand. ..
  2. Palacios G, Muro A, Vela J, Molina Holgado E, Guitart X, Ovalle S, et al. Immunohistochemical localization of the sigma1-receptor in oligodendrocytes in the rat central nervous system. Brain Res. 2003;961:92-9 pubmed
    ..These results suggest that sigma(1)-receptor in oligodendrocytes might be involved in myelination by direct implication in cholesterol biosynthesis or by interaction with endogenous ligands such as neurosteroids. ..
  3. Palacios G, Muro A, Verdú E, Pumarola M, Vela J. Immunohistochemical localization of the sigma1 receptor in Schwann cells of rat sciatic nerve. Brain Res. 2004;1007:65-70 pubmed
  4. Zhang H, Cuevas J. Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons. J Neurophysiol. 2002;87:2867-79 pubmed
    ..Activation of sigma receptors on sympathetic and parasympathetic neurons is likely to modulate cell-to-cell signaling in autonomic ganglia and thus the regulation of cardiac function by the peripheral nervous system...
  5. Tsai S, Hayashi T, Harvey B, Wang Y, Wu W, Shen R, et al. Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1xGTP pathway. Proc Natl Acad Sci U S A. 2009;106:22468-73 pubmed publisher
    ..These results implicate Sig-1Rs as endogenous regulators of hippopcampal dendritic spine formation and suggest a free radical-sensitive ER-mitochondrion-Rac1.GTP pathway in the regulation of dendritic spine formation in the hippocampus. ..
  6. Mei J, Pasternak G. Modulation of brainstem opiate analgesia in the rat by sigma 1 receptors: a microinjection study. J Pharmacol Exp Ther. 2007;322:1278-85 pubmed
    ..These studies illustrate the pharmacological importance of sigma(1) receptors in the brainstem modulation of opioid analgesia. ..
  7. Hayashi T, SU T. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell. 2007;131:596-610 pubmed
    ..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. ..
  8. Kourrich S, Hayashi T, Chuang J, Tsai S, SU T, Bonci A. Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine. Cell. 2013;152:236-47 pubmed publisher
    ..Functional consequences of Sig-1R binding to K(+) channels may have implications for other chronic diseases where maladaptive intrinsic plasticity and Sig-1Rs are engaged. ..
  9. Schmidt H, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse A. Crystal structure of the human ?1 receptor. Nature. 2016;532:527-30 pubmed publisher
    ..Taken together, these results reveal the overall architecture, oligomerization state, and molecular basis for ligand recognition by this important but poorly understood protein. ..
  10. Blasio A, Valenza M, Iyer M, Rice K, Steardo L, Hayashi T, et al. Sigma-1 receptor mediates acquisition of alcohol drinking and seeking behavior in alcohol-preferring rats. Behav Brain Res. 2015;287:315-22 pubmed publisher
    ..Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction. ..
  11. Klouz A, Saïd D, Ferchichi H, Kourda N, Ouanes L, Lakhal M, et al. Protection of cellular and mitochondrial functions against liver ischemia by N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), a sigma1 ligand. Eur J Pharmacol. 2008;578:292-9 pubmed
    ..These data demonstrate that BHDP protects liver against the deleterious effects of ischemia-reperfusion and suggest that sigma(1) receptors play an important role in the protective effect. ..
  12. Bhuiyan S, Fukunaga K. Stimulation of Sigma-1 receptor by dehydroepiandrosterone ameliorates hypertension-induced kidney hypertrophy in ovariectomized rats. Exp Biol Med (Maywood). 2010;235:356-64 pubmed publisher
    ..DHEA administration protects hypertension-induced kidney injury via upregulation of Sigma-1R and stimulation of Akt-eNOS signaling in ovariectomized rats. ..
  13. Prause J, Goswami A, Katona I, Roos A, Schnizler M, Bushuven E, et al. Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2013;22:1581-600 pubmed publisher
    ..Finally, pharmacological activation of SigR1 induced the clearance of mutant protein aggregates in these cells. Our results support the notion that SigR1 is abnormally modified and contributes to the pathogenesis of ALS. ..
  14. Tagashira H, Matsumoto T, Taguchi K, Zhang C, Han F, Ishida K, et al. Vascular endothelial ?1-receptor stimulation with SA4503 rescues aortic relaxation via Akt/eNOS signaling in ovariectomized rats with aortic banding. Circ J. 2013;77:2831-40 pubmed
    ..These observations encourage development of novel therapeutics targeting ?1R to prevent vascular endothelial injury in vascular diseases. ..
  15. Choi S, Roh D, Yoon S, Kang S, Moon J, Kwon S, et al. Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats. Pharmacol Res. 2013;74:56-67 pubmed publisher
  16. Wu Z, Li L, Zheng L, Xu Z, Guo L, Zhen X. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. J Neurochem. 2015;134:904-14 pubmed publisher
  17. Langa F, Codony X, Tovar V, Lavado A, Giménez E, Cozar P, et al. Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice. Eur J Neurosci. 2003;18:2188-96 pubmed
    ..The activity of sigma 2-receptors seems to be unaffected in sigma 1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors. ..
  18. Zhang X, Liu L, Wu Y, Jiang S, Zhong Y, Yang X. ? receptor 1 is preferentially involved in modulation of N-methyl-D-aspartate receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells. Neurosignals. 2011;19:110-6 pubmed publisher
    ..These results suggest that ?R1 may be involved in the regulation of output signaling of GCs by preferentially modulating NMDA receptor-mediated eEPSCs of these retinal neurons. ..
  19. Du K, Wang X, Chi L, Li W. Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain. Anesth Analg. 2017;125:662-669 pubmed publisher
    ..The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats. ..
  20. Jbilo O, Vidal H, Paul R, De Nys N, Bensaid M, Silve S, et al. Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. J Biol Chem. 1997;272:27107-15 pubmed
    ..Taken together, these findings strongly suggest that SR-BP represents the molecular target for SR 31747A in mammalian tissues, which could be critical for T cell proliferation. ..
  21. Moradpour F, Fathollahi Y, Naghdi N, Hosseinmardi N, Javan M. Prepubertal castration-associated developmental changes in sigma-1 receptor gene expression levels regulate hippocampus area CA1 activity during adolescence. Hippocampus. 2016;26:933-46 pubmed publisher
    ..2016 Wiley Periodicals, Inc. ..
  22. Sabino V, Cottone P, Blasio A, Iyer M, Steardo L, Rice K, et al. Activation of ?-receptors induces binge-like drinking in Sardinian alcohol-preferring rats. Neuropsychopharmacology. 2011;36:1207-18 pubmed publisher
    ..These results suggest a key facilitatory role for ?-receptors in the reinforcing effects of alcohol and identify a potential mechanism that contributes to binge-like and excessive drinking. ..
  23. Sabeti J. Ethanol exposure in early adolescence inhibits intrinsic neuronal plasticity via sigma-1 receptor activation in hippocampal CA1 neurons. Alcohol Clin Exp Res. 2011;35:885-904 pubmed publisher
    ..Such withdrawal-induced depression of E-S plasticity in hippocampus probably entails sigma-1 receptor modulation of 1 or several voltage-gated ion channels controlling the neuronal input-output dynamics. ..
  24. Liu L, Deng Q, Weng S, Yang X, Zhong Y. Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells. Neuroscience. 2016;332:53-60 pubmed publisher
    ..We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. ..
  25. Mavlyutov T, Epstein M, Andersen K, Ziskind Conhaim L, Ruoho A. The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study. Neuroscience. 2010;167:247-55 pubmed publisher
    ..Together these data indicate that the sigma-1 receptor may play a role in the regulation of motor behavior. ..
  26. Dussossoy D, Carayon P, Belugou S, Feraut D, Bord A, Goubet C, et al. Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level. Eur J Biochem. 1999;263:377-86 pubmed
    ..Taken together our results suggest that both SR31747A-binding proteins not only play a role in sterol metabolism but indirectly affect lipoprotein functions. ..
  27. Martin Fardon R, Strong E, Weiss F. Effect of ?? receptor antagonism on ethanol and natural reward seeking. Neuroreport. 2012;23:809-13 pubmed publisher
  28. Mavlyutov T, Duellman T, Kim H, Epstein M, Leese C, Davletov B, et al. Sigma-1 receptor expression in the dorsal root ganglion: Reexamination using a highly specific antibody. Neuroscience. 2016;331:148-57 pubmed publisher
  29. Bao Q, Zhao M, Chen L, Wang Y, Wu S, Wu W, et al. MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor. Life Sci. 2017;175:1-10 pubmed publisher
    ..Our data demonstrate that miR-297 promotes cardiomyocyte hypertrophy by inhibiting the expression of Sig-1R and activation of ER stress signaling, which provides a novel interpretation for cardiac hypertrophy. ..
  30. FONTANILLA D, Johannessen M, Hajipour A, Cozzi N, Jackson M, Ruoho A. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science. 2009;323:934-7 pubmed publisher
    ..DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. ..
  31. Sabino V, Cottone P, Zhao Y, Iyer M, Steardo L, Rice K, et al. The sigma-receptor antagonist BD-1063 decreases ethanol intake and reinforcement in animal models of excessive drinking. Neuropsychopharmacology. 2009;34:1482-93 pubmed publisher
  32. Bangaru M, Weihrauch D, Tang Q, Zoga V, Hogan Q, Wu H. Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury. Mol Pain. 2013;9:47 pubmed publisher
    ..This implies that increased levels of endogenous ?1R agonists may play a role, and diminished neuroprotection from loss of glial ?1R may be a contributing factor. ..
  33. Ola M, Moore P, el Sherbeny A, Roon P, Agarwal N, Sarthy V, et al. Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina. Brain Res Mol Brain Res. 2001;95:86-95 pubmed
    ..Our findings suggest that retinal ganglion cells may be amenable to the neuroprotective effects of sigma ligands under conditions of neurotoxicity such as occurs in diabetes. ..
  34. Fu Y, Zhao Y, Luan W, Dong L, Dong Y, Lai B, et al. Sigma-1 receptors amplify dopamine D1 receptor signaling at presynaptic sites in the prelimbic cortex. Biochim Biophys Acta. 2010;1803:1396-408 pubmed publisher
    ..These results suggest that sigma-1 receptors may amplify the D1 receptor agonist-induced PKA activation by sigma-1 receptors - cPKC (especially the PKC?I) - L-type Ca(2+) channels - Ca(2+) - AC and/or cAMP signaling pathway...
  35. Alam S, Abdullah C, Aishwarya R, Orr A, Traylor J, Miriyala S, et al. Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes. Biosci Rep. 2017;37: pubmed publisher
    ..Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes...
  36. Eraso Pichot A, Larramona Arcas R, Vicario Orri E, Villalonga R, Pardo L, Galea E, et al. CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor. Cell Mol Life Sci. 2017;74:937-950 pubmed publisher
    ..We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression. ..
  37. Tomohisa M, Junpei O, Aki M, Masato H, Mika F, Kazumi Y, et al. Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain. Synapse. 2015;69:526-32 pubmed publisher
    ..These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. ..
  38. Al Saif A, Al Mohanna F, Bohlega S. A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol. 2011;70:913-9 pubmed publisher
    ..3 containing 9 RefSeq genes. Sequencing the SIGMAR1 gene revealed a mutation affecting a highly conserved amino acid located in the transmembrane domain of the ..
  39. Liu L, Wang L, Zhong Y, Yang X. Expression of sigma receptor 1 mRNA and protein in rat retina. Neuroscience. 2010;167:1151-9 pubmed publisher
    ..Two types of sigmaRs have been identified: sigmaR1 and sigmaR2...
  40. Hayashi T, Hayashi E, Fujimoto M, Sprong H, SU T. The lifetime of UDP-galactose:ceramide galactosyltransferase is controlled by a distinct endoplasmic reticulum-associated degradation (ERAD) regulated by sigma-1 receptor chaperones. J Biol Chem. 2012;287:43156-69 pubmed publisher
    ..The GalCer synthesis may thus be influenced by sterols at the ER. ..
  41. Tsai S, Rothman R, SU T. Insights into the Sigma-1 receptor chaperone's cellular functions: a microarray report. Synapse. 2012;66:42-51 pubmed publisher
    ..These data further confirmed that Sig-1Rs play critical roles in the CNS and thus these findings may aid in future development of therapeutic treatments targeting neurodegenerative disorders. ..
  42. Yagasaki Y, Numakawa T, Kumamaru E, Hayashi T, SU T, Kunugi H. Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release. J Biol Chem. 2006;281:12941-9 pubmed
    ..These results suggest that antidepressant pretreatment selectively enhance the BDNF signaling on the PLC-gamma/IP3/Ca2+ pathway via Sig-1R, and that Sig-1R plays an important role in BDNF signaling leading to glutamate release. ..
  43. Ishima T, Fujita Y, Hashimoto K. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells. Eur J Pharmacol. 2014;727:167-73 pubmed publisher
    ..In contrast, mirtazapine independently potentiated neurite outgrowth in PC12 cells, indicating that this beneficial effect may mediate its pharmacological effect. ..
  44. Herrera Y, Katnik C, Rodriguez J, Hall A, Willing A, Pennypacker K, et al. sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a-induced Ca2+ influx in rat cortical neurons. J Pharmacol Exp Ther. 2008;327:491-502 pubmed publisher
    ..The ability to control ionic imbalances and Ca2+ dysregulation evoked by ASIC1a activation makes sigma receptors an attractive target for ischemic stroke therapy. ..
  45. Ramakrishnan N, Marosi K, Nyakas C, Kwizera C, Elsinga P, Ishiwata K, et al. Altered sigma-1 receptor expression in two animal models of cognitive impairment. Mol Imaging Biol. 2015;17:231-8 pubmed publisher
    ..Cholinergic lesioning causes an increase of sigma-1 receptor expression in a small cortical area which may be neuroprotective. Sleep deprivation decreases receptor expression in midbrain and pons. ..
  46. Ka M, Kook Y, Liao K, Buch S, Kim W. Transactivation of TrkB by Sigma-1 receptor mediates cocaine-induced changes in dendritic spine density and morphology in hippocampal and cortical neurons. Cell Death Dis. 2016;7:e2414 pubmed publisher
  47. Lu C, Lin T, Wang C, Wang S. ?-1 Receptor agonist SKF10047 inhibits glutamate release in rat cerebral cortex nerve endings. J Pharmacol Exp Ther. 2012;341:532-42 pubmed publisher
    ..This effect is linked to a decrease in [Ca²?](C) caused by Ca²? entry through presynaptic voltage-dependent Ca²? channels and the suppression of the PKC signaling cascade. ..
  48. Hong W, Yano H, Hiranita T, Chin F, McCurdy C, SU T, et al. The sigma-1 receptor modulates dopamine transporter conformation and cocaine binding and may thereby potentiate cocaine self-administration in rats. J Biol Chem. 2017;292:11250-11261 pubmed publisher
    ..We propose that this novel molecular mechanism underlies the behavioral potentiation of cocaine self-administration by ?1R agonists in animal models. ..