M J Lohse

Summary

Country: Germany

Publications

  1. pmc Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells
    Mark C Harbeck
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Sci STKE 2006:pl6. 2006
  2. doi request reprint Blocking them all: beta-arrestins inhibit cellular signaling
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Mol Cell 31:619-21. 2008
  3. ncbi request reprint Gs activation is time-limiting in initiating receptor-mediated signaling
    Peter Hein
    University Wurzburg, Institute of Pharmacology and Toxicology, Versbacher Strasse 9, 97078 Wurzburg, Germany
    J Biol Chem 281:33345-51. 2006
  4. ncbi request reprint Kinetics and mechanism of G protein-coupled receptor activation
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, 97078 Wurzburg, Germany Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, 97078 Wurzburg, Germany Electronic address
    Curr Opin Cell Biol 27:87-93. 2014
  5. doi request reprint Arrestin interactions with G protein-coupled receptors
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Straße 9, 97078, Wurzburg, Germany
    Handb Exp Pharmacol 219:15-56. 2014
  6. doi request reprint The guanine nucleotide exchange factor Vav2 is a negative regulator of parathyroid hormone receptor/Gq signaling
    Alexander Emami-Nemini
    Institute of Pharmacology and Toxicology, Rudolf Virchow Center, University of Wurzburg, Versbacher Straße 9, Wurzburg, Germany
    Mol Pharmacol 82:217-25. 2012
  7. doi request reprint Nonequilibrium activation of a G-protein-coupled receptor
    Manuela Ambrosio
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Mol Pharmacol 81:770-7. 2012
  8. doi request reprint Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling
    Martin J Lohse
    Institute of Pharmacology and Toxicology, Versbacher Str 9, 97078 Wurzburg, Germany
    Pharmacol Rev 64:299-336. 2012
  9. pmc Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base
    Lucy Skrabanek
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    BMC Bioinformatics 8:177. 2007
  10. ncbi request reprint What is the role of beta-adrenergic signaling in heart failure?
    Martin J Lohse
    Institute of Pharmacology, Versbacher Strasse 9, 97078 Wuerzburg, Germany
    Circ Res 93:896-906. 2003

Detail Information

Publications109 found, 100 shown here

  1. pmc Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells
    Mark C Harbeck
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Sci STKE 2006:pl6. 2006
    ..This real-time imaging method allows investigation of the dynamic organization and integration of multiple levels of signal processing in single living cells...
  2. doi request reprint Blocking them all: beta-arrestins inhibit cellular signaling
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Mol Cell 31:619-21. 2008
    ..In this issue of Molecular Cell, Mo et al. (2008) show that beta-arrestin1 also switches off signaling through the STAT1 transcription factor, thereby inhibiting interferon-induced antiviral responses...
  3. ncbi request reprint Gs activation is time-limiting in initiating receptor-mediated signaling
    Peter Hein
    University Wurzburg, Institute of Pharmacology and Toxicology, Versbacher Strasse 9, 97078 Wurzburg, Germany
    J Biol Chem 281:33345-51. 2006
    ..Taken together, our kinetic measurements demonstrate that the rate of G(S) activation limits initiation of G(S)-coupled receptor signaling...
  4. ncbi request reprint Kinetics and mechanism of G protein-coupled receptor activation
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, 97078 Wurzburg, Germany Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, 97078 Wurzburg, Germany Electronic address
    Curr Opin Cell Biol 27:87-93. 2014
    ....
  5. doi request reprint Arrestin interactions with G protein-coupled receptors
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Straße 9, 97078, Wurzburg, Germany
    Handb Exp Pharmacol 219:15-56. 2014
    ....
  6. doi request reprint The guanine nucleotide exchange factor Vav2 is a negative regulator of parathyroid hormone receptor/Gq signaling
    Alexander Emami-Nemini
    Institute of Pharmacology and Toxicology, Rudolf Virchow Center, University of Wurzburg, Versbacher Straße 9, Wurzburg, Germany
    Mol Pharmacol 82:217-25. 2012
    ..Our results show that a RhoA GEF can specifically interact with a GPCR and modulate its G protein signaling specificity...
  7. doi request reprint Nonequilibrium activation of a G-protein-coupled receptor
    Manuela Ambrosio
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Mol Pharmacol 81:770-7. 2012
    ....
  8. doi request reprint Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling
    Martin J Lohse
    Institute of Pharmacology and Toxicology, Versbacher Str 9, 97078 Wurzburg, Germany
    Pharmacol Rev 64:299-336. 2012
    ..We review here the FRET and BRET technologies that have been developed for G-protein-coupled receptors and their signaling proteins (G-proteins, effectors) and the concepts that result from such experiments...
  9. pmc Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base
    Lucy Skrabanek
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    BMC Bioinformatics 8:177. 2007
    ....
  10. ncbi request reprint What is the role of beta-adrenergic signaling in heart failure?
    Martin J Lohse
    Institute of Pharmacology, Versbacher Strasse 9, 97078 Wuerzburg, Germany
    Circ Res 93:896-906. 2003
    ..Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps...
  11. ncbi request reprint Kinetics of G-protein-coupled receptor signalling and desensitization
    C Krasel
    Institute for Pharmacology and Toxicology, Versbacher Str 9, D 97078 Wurzburg, Germany
    Biochem Soc Trans 32:1029-31. 2004
    ..Using these methods, we show that receptor activation by agonists and signalling to G-proteins occur on the subsecond time scale, whereas receptor desensitization is limited by receptor phosphorylation and proceeds more slowly...
  12. doi request reprint Optical techniques to analyze real-time activation and signaling of G-protein-coupled receptors
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Trends Pharmacol Sci 29:159-65. 2008
    ..They are also raising controversial issues, such as whether or not receptors and G proteins are pre-coupled and whether G proteins dissociate during activation...
  13. ncbi request reprint Beta-adrenoceptor polymorphisms and heart failure
    Martin J Lohse
    Institue for Pharmacology and Toxicology, University of Wuerzburg, Germany
    Trends Mol Med 10:55-8. 2004
    ....
  14. doi request reprint Dimerization in GPCR mobility and signaling
    Martin J Lohse
    Institute of Pharmacology and Toxicology, Wurzburg, Germany
    Curr Opin Pharmacol 10:53-8. 2010
    ..However, dimerization may serve to affect receptor mobility at the cell surface and in intracellular trafficking, and may be involved in and affect their signaling functions...
  15. ncbi request reprint Direct optical recording of intrinsic efficacy at a G protein-coupled receptor
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str 9, D 97078, Wurzburg, Germany
    Life Sci 74:397-404. 2003
    ..Thus, optical recording of the agonist-induced conformational change in a G-protein-coupled receptor allows the direct analysis of the intrinsic efficacies of agonists...
  16. pmc Kinetics of G-protein-coupled receptor signals in intact cells
    M J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Br J Pharmacol 153:S125-32. 2008
    ..This review summarizes recent findings illustrating the speed and the complexity of this signalling system...
  17. ncbi request reprint Monitoring receptor signaling by intramolecular FRET
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str 9, 97078 Wurzburg, Germany
    Curr Opin Pharmacol 7:547-53. 2007
    ..Here, we review the latter approach as a tool to study receptor activation and the levels of the second messengers cAMP and cGMP in intact cells...
  18. ncbi request reprint Probing human beta 1- and beta 2-adrenoceptors with domain-specific fusion protein antibodies
    R Jahns
    Department of Pharmacology, University of Wurzburg, Germany
    Eur J Pharmacol 316:111-21. 1996
    ....
  19. ncbi request reprint Differential conformational requirements for activation of G proteins and the regulatory proteins arrestin and G protein-coupled receptor kinase in the G protein-coupled receptor for parathyroid hormone (PTH)/PTH-related protein
    J P Vilardaga
    Department of Pharmacology, Institute of Pharmacology and Toxicology, University of Wurzburg, D 97078 Wurzburg, Germany
    J Biol Chem 276:33435-43. 2001
    ..Furthermore, PTHR sequestration does not appear to require G protein activation...
  20. ncbi request reprint Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association
    Jean Pierre Vilardaga
    Department of Pharmacology, Institute of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg D 97078, Germany
    J Biol Chem 277:8121-9. 2002
    ..Determinants in the receptor's core (Asn-289 and Lys-382) appear to regulate internalization of the receptor/beta-arrestin complex toward early endocytic endosomes during the initial step of endocytosis...
  21. ncbi request reprint Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents
    M Bunemann
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    J Biol Chem 276:47512-7. 2001
    ....
  22. doi request reprint Fluorescence resonance energy transfer analysis of alpha 2a-adrenergic receptor activation reveals distinct agonist-specific conformational changes
    A Zurn
    Universitat Wurzburg, Institute of Pharmacology and Toxicology, Wurzburg, Germany
    Mol Pharmacol 75:534-41. 2009
    ....
  23. ncbi request reprint G Protein activation without subunit dissociation depends on a G{alpha}(i)-specific region
    Monika Frank
    Department of Pharmacology and Toxicology, The University of Würzburg, 97078 Wurzburg, Germany
    J Biol Chem 280:24584-90. 2005
    ..The discovery of subtype-selective mechanisms of G protein activation illustrates that G protein subfamilies have specific mechanisms of activation that may provide a previously unknown basis for G protein signaling specificity...
  24. pmc Temporally resolved cAMP monitoring in endothelial cells uncovers a thrombin-induced [cAMP] elevation mediated via the Ca²+-dependent production of prostacyclin
    R C Werthmann
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacherstrasse 9, 97078 Wurzburg, Germany
    J Physiol 589:181-93. 2011
    ..We conclude that thrombin causes the synthesis of prostacyclin in endothelial cells and that the subsequent stimulation of Gs-coupled prostacyclin receptors then results in an increase in [cAMP]...
  25. ncbi request reprint SUMO-1 controls the protein stability and the biological function of phosducin
    Christoph Klenk
    Institute of Pharmacology, University of Wurzburg, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 281:8357-64. 2006
    ..Together, these findings show that phosducin is a previously unrecognized target of SUMO modification and that SUMOylation controls phosducin stability in cells as well as its functional properties...
  26. doi request reprint Gq-mediated Ca2+ signals inhibit adenylyl cyclases 5/6 in vascular smooth muscle cells
    Kathrin von Hayn
    University of Marburg, Institute of Pharmacology and Toxicology, Karl von Frisch Strasse 1, 35033 Marburg, Germany
    Am J Physiol Cell Physiol 298:C324-32. 2010
    ..Taken together, these results implicate a Ca(2+)-mediated inhibition of AC5 and 6 as an important mechanism of purinergic receptor-induced decline of cAMP and show a direct cross talk of these signaling pathways in VSMCs...
  27. ncbi request reprint Probing human beta1- and beta2 -adrenoceptors with domain-specific fusion protein antibodies
    R Jahns
    Department of Pharmacology, University of Wurzburg, Germany
    Eur J Pharmacol 334:115-26. 1997
    ....
  28. pmc Conformational changes in G-protein-coupled receptors-the quest for functionally selective conformations is open
    C Hoffmann
    Institut of Pharmacology and Toxicology, Universitat Wurzburg, Wurzburg, Germany
    Br J Pharmacol 153:S358-66. 2008
    ..In this review we will summarize recent progress in biophysical approaches that have led to the current understanding of conformational changes that occur during GPCR activation...
  29. doi request reprint beta-Arrestin-2 interaction and internalization of the human P2Y1 receptor are dependent on C-terminal phosphorylation sites
    Susanne Reiner
    Department of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Str 9, 97078 Wuerzburg, Germany
    Mol Pharmacol 76:1162-71. 2009
    ..Thus, we conclude that P2Y(1)-receptor desensitization and internalization are mediated by different phosphorylation sites and kinases...
  30. ncbi request reprint Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching beta1-adrenergic but locally confined beta2-adrenergic receptor-mediated signaling
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology, University of Wuerzburg, Germany
    Circ Res 99:1084-91. 2006
    ..Our data reveal that in adult cardiac myocytes, beta(1)ARs induce far-reaching cAMP signals, whereas beta(2)AR-induced cAMP remains locally confined...
  31. ncbi request reprint Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells
    C Hoffmann
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 369:151-9. 2004
    ..These specific mixtures of agonism, antagonism, and inverse agonism at different subtypes may have important implications for the therapeutic use of the respective compounds...
  32. ncbi request reprint Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation
    Cornelius Krasel
    Institute for Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 280:9528-35. 2005
    ..This fast agonist-controlled association and dissociation of beta-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity in repeatedly stimulated cells such as neurons...
  33. ncbi request reprint Phosducin-like protein regulates G-protein betagamma folding by interaction with tailless complex polypeptide-1alpha: dephosphorylation or splicing of PhLP turns the switch toward regulation of Gbetagamma folding
    Jan Humrich
    Institute of Pharmacology and Toxicology, University of Wuerzburg, Germany
    J Biol Chem 280:20042-50. 2005
    ..We therefore conclude that the strong inhibitory action of PhLP(S) on Gbetagamma signaling is the result of a previously unrecognized mechanism of Gbetagamma-regulation, inhibition of Gbetagamma-folding by interference with TCP-1alpha...
  34. doi request reprint Dual role of the beta2-adrenergic receptor C terminus for the binding of beta-arrestin and receptor internalization
    Cornelius Krasel
    Institute of Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wuerzburg, Germany
    J Biol Chem 283:31840-8. 2008
    ..Our experiments show that the C terminus distal to residue 381 does not affect the initial interaction between receptor and beta-arrestin, but its last eight amino acids facilitate receptor internalization in concert with beta-arrestin2...
  35. ncbi request reprint A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells
    Carsten Hoffmann
    Institute of Pharmacology and Toxicology, University of Wurzburg, Germany
    Nat Methods 2:171-6. 2005
    ..Thus, FRET from CFP to FlAsH reports GPCR activation in living cells without disturbing receptor function and shows that the small size of the tetracysteine-biarsenical tag can be decisively advantageous...
  36. pmc A fluorescence resonance energy transfer-based M2 muscarinic receptor sensor reveals rapid kinetics of allosteric modulation
    Monika Maier-Peuschel
    Institute of Pharmacology and Toxicology and the Rudolf Virchow Center, University of Wurzburg, 97078 Wurzburg, Germany
    J Biol Chem 285:8793-800. 2010
    ....
  37. doi request reprint Analysis of receptor oligomerization by FRAP microscopy
    Sandra Dorsch
    University of Wurzburg, Institute of Pharmacology and Toxicology, Versbacher Strasse 9, Wurzburg, Germany
    Nat Methods 6:225-30. 2009
    ..We propose that this FRAP method can be widely applied to study di- or oligomerization of cell-surface proteins...
  38. doi request reprint Real-time monitoring of somatostatin receptor-cAMP signaling in live pituitary
    Stefan Jacobs
    Institute of Pharmacology and Toxicology, University of Wurzburg, 97078 Wurzburg, Germany
    Endocrinology 151:4560-5. 2010
    ..This technique can be widely used to assess the contribution of various pituitary receptors, including individual G(i) protein-coupled somatostatin receptors, to the regulation of cAMP levels under physiologically relevant settings...
  39. ncbi request reprint Modulation of beta1-adrenoceptor activity by domain-specific antibodies and heart failure-associated autoantibodies
    R Jahns
    Department of Internal Medicine, Medizinische Poliklinik, University of Wuerzburg, Germany
    J Am Coll Cardiol 36:1280-7. 2000
    ..Our study attempted to gain further understanding of the allosteric effects of human autoantibodies on beta1-adrenergic receptor (beta1-AR) function...
  40. ncbi request reprint Acute changes of myocardial creatine kinase gene expression under beta-adrenergic stimulation
    S Hammerschmidt
    Department of Medicine Pharmacology, University of Wurzburg, Wurzburg, Germany
    Biochim Biophys Acta 1502:471-80. 2000
    ..This may be interpreted as an adaptive mechanism making energy transduction via CK more efficient at times of increased metabolic demand...
  41. pmc Real-time monitoring of cAMP levels in living endothelial cells: thrombin transiently inhibits adenylyl cyclase 6
    R C Werthmann
    Department of Pharmacology and Toxicology, University of Wurzburg, Versbacherstrasse 9, 97078 Wurzburg, Germany
    J Physiol 587:4091-104. 2009
    ..Instead the knock down of the predominant subtype AC6 in HUVECs provided the first direct evidence that the Ca(2+)-mediated inhibition of AC6 accounts for the thrombin-induced decrease in cAMP levels...
  42. ncbi request reprint Activating beta-1-adrenoceptor antibodies are not associated with cardiomyopathies secondary to valvular or hypertensive heart disease
    R Jahns
    Department of Internal Medicine, Medizinische Poliklinik, University of Wuerzburg, Germany
    J Am Coll Cardiol 34:1545-51. 1999
    ..We investigated whether autoantibodies against the human beta-adrenergic receptor (beta-AR) might be involved in cardiomyopathies secondary to valvular heart disease (VHD) or hypertensive heart disease (HHD)...
  43. ncbi request reprint Dobutamine-stress magnetic resonance microimaging in mice : acute changes of cardiac geometry and function in normal and failing murine hearts
    F Wiesmann
    Medizinische Universitätsklinik Würzburg, Germany
    Circ Res 88:563-9. 2001
    ..This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure...
  44. ncbi request reprint A novel fluorescence method for the rapid detection of functional beta1-adrenergic receptor autoantibodies in heart failure
    Viacheslav O Nikolaev
    Institut fur Pharmakologie und Toxikologie, University of Wurzburg, Wurzburg, Germany
    J Am Coll Cardiol 50:423-31. 2007
    ..This study sought to develop a rapid method for the detection of activating autoantibodies directed against the beta1-adrenoceptor (anti-beta1-Abs) in patients with heart failure...
  45. pmc Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol
    Francesca Rochais
    Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
    J Clin Invest 117:229-35. 2007
    ..It revealed that beta(1)-AR variants dramatically differ in their responses to diverse beta blockers, with possible consequences for their clinical use...
  46. ncbi request reprint Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy
    Stefan Störk
    Department of Internal Medicine I Center of Cardiovascular Medicine, University of Wurzburg, Wurzburg, Germany
    Am Heart J 152:697-704. 2006
    ....
  47. ncbi request reprint Beta 1-adrenergic receptor-directed autoimmunity as a cause of dilated cardiomyopathy in rats
    Roland Jahns
    Department of Internal Medicine, Medizinische Klinik und Poliklinik I, University of Wuerzburg, Josef Schneider Strasse 2, D 97080 Wuerzburg, Germany
    Int J Cardiol 112:7-14. 2006
    ....
  48. doi request reprint A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy
    Kristina Lorenz
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, Wurzburg, Germany
    Nat Med 15:75-83. 2009
    ..We propose that specific phosphorylation events on ERK1/2 integrate differing upstream signals (Raf1-MEK1/2 or G protein-coupled receptor-G(q)) to induce cardiac hypertrophy...
  49. doi request reprint Cardiac hypertrophy: targeting Raf/MEK/ERK1/2-signaling
    Kristina Lorenz
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Int J Biochem Cell Biol 41:2351-5. 2009
    ..This short review will discuss new mechanistic insights into ERK1/2-dependent development of cardiac hypertrophy and the prospect to translate this knowledge into future therapeutic strategies...
  50. doi request reprint Targeting receptor antibodies in immune cardiomyopathy
    Roland Jahns
    Department of Internal Medicine, Medizinische Klinik und Poliklinik I, Cardiology, Germany
    Semin Thromb Hemost 36:212-8. 2010
    ..Elimination by (extracorporeal) immunoadsorption or direct neutralization of the harmful receptor autoantibodies in the circulating blood represent promising strategies to protect the heart from beta1-(auto)antibody-induced damage...
  51. pmc Agonist-selective, receptor-specific interaction of human P2Y receptors with beta-arrestin-1 and -2
    Carsten Hoffmann
    Institute for Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wuerzburg, Germany
    J Biol Chem 283:30933-41. 2008
    ..This suggests that the two different agonists induce distinct active states of this receptor that show differential interactions with beta-arrestins...
  52. doi request reprint Imaging of persistent cAMP signaling by internalized G protein-coupled receptors
    Davide Calebiro
    Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
    J Mol Endocrinol 45:1-8. 2010
    ..Based on these findings, we propose a revision of the current model of the GPCR-cAMP signaling pathway to accommodate receptor signaling at endosomes...
  53. pmc Agonist-regulated cleavage of the extracellular domain of parathyroid hormone receptor type 1
    Christoph Klenk
    Institute of Pharmacology and Toxicology, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Wrzburg, 97078 Wurzburg, Germany
    J Biol Chem 285:8665-74. 2010
    ..A processed form of the PTHR was also detected in human kidney. These findings suggest a new model of PTHR processing and regulation of its stability...
  54. doi request reprint Signaling by internalized G-protein-coupled receptors
    Davide Calebiro
    Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
    Trends Pharmacol Sci 31:221-8. 2010
    ..We propose that current models of GPCR signaling should be revised to accommodate the ability of receptors to change their signaling properties depending on their subcellular localization...
  55. doi request reprint Alterations of phospholamban function can exhibit cardiotoxic effects independent of excessive sarcoplasmic reticulum Ca2+-ATPase inhibition
    Joachim P Schmitt
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Circulation 119:436-44. 2009
    ..Here, we investigated whether PLN exhibits cardiotoxic effects via mechanisms other than chronic inhibition of SERCA2a by studying a PLN mutant, PLN(R9C), that triggers cardiac failure in humans and mice...
  56. ncbi request reprint Live cell monitoring of mu-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology and Bio Imaging Center, University of Wurzburg, Versbacherstrasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 282:27126-32. 2007
    ..Taken together, our data indicate that FRET-based assays of G-protein activation can serve to determine the abilities of compounds to activate G-protein signaling directly and in living cells...
  57. ncbi request reprint Monitoring of cAMP synthesis and degradation in living cells
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    Physiology (Bethesda) 21:86-92. 2006
    ..In this review, we describe and compare these techniques in terms of their robustness, sensitivity and spatio-temporal resolution...
  58. ncbi request reprint Alterations in the myocardial creatine kinase system precede the development of contractile dysfunction in beta(1)-adrenergic receptor transgenic mice
    Matthias Spindler
    Medizinische Universitätsklinik Würzburg, Universitat Wurzburg, Josef Schneider Strasse 2, 97080 Wuerzburg, Germany
    J Mol Cell Cardiol 35:389-97. 2003
    ....
  59. pmc Gi protein activation in intact cells involves subunit rearrangement rather than dissociation
    Moritz Bünemann
    Department of Pharmacology and Toxicology, University of Wurzburg, Versbacherstrasse 9, 97078 Wurzburg, Germany
    Proc Natl Acad Sci U S A 100:16077-82. 2003
    ..This finding will be of particular interest for unraveling Gbetagamma-induced signaling pathways...
  60. ncbi request reprint Altered calcium handling is critically involved in the cardiotoxic effects of chronic beta-adrenergic stimulation
    Stefan Engelhardt
    Institute of Pharmacology and Toxicology, of Wuerzburg, Germany
    Circulation 109:1154-60. 2004
    ..We investigated whether genetic modification of calcium handling through deletion of phospholamban in mice would affect the development of heart failure in mice with transgenic overexpression of the beta1-adrenergic receptor...
  61. ncbi request reprint Self-limitation of intravenous tocolysis with beta2-adrenergic agonists is mediated through receptor G protein uncoupling
    Torsten Frambach
    Department of Obstetrics and Gynecology and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Bayerische Julius Maximilians Universität Würzburg, Wurzburg, Germany
    J Clin Endocrinol Metab 90:2882-7. 2005
    ..In addition to the known reduction in receptor number (down-regulation) as underlying mechanism, uncoupling of the receptor from the stimulatory G protein G(s) was identified...
  62. pmc Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy
    Roland Jahns
    Department of Pharmacology and Toxicology, Medizinische Poliklinik, University of Wuerzburg, Germany
    J Clin Invest 113:1419-29. 2004
    ..Although carried out in an experimental animal model, our findings should further encourage the development of therapeutic strategies that combat harmful anti-beta(1)-EC(II) in receptor Ab-positive DCM patients...
  63. ncbi request reprint beta(1)-Adrenergic receptor function, autoimmunity, and pathogenesis of dilated cardiomyopathy
    Roland Jahns
    Department of Internal Medicine, Medizinische Klinik und Poliklinik I, University of Wurzburg, D 97080 Wurzburg, Germany
    Trends Cardiovasc Med 16:20-4. 2006
    ..This article reviews current knowledge and recent experimental and clinical findings focusing on the role of the beta(1)-adrenergic receptor as a self-antigen in the pathogenesis of DCM...
  64. ncbi request reprint Molecular basis of inverse agonism in a G protein-coupled receptor
    Jean Pierre Vilardaga
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    Nat Chem Biol 1:25-8. 2005
    ..This switch couples inverse agonist binding to the suppression of activity in the receptor...
  65. ncbi request reprint Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin
    C Krasel
    Institut fur Pharmakologie und Toxikologie, Versbacher Str 9, D 97078 Wurzburg, Germany
    J Biol Chem 276:1911-5. 2001
    ..This inhibition was almost completely abolished in vitro when GRK2 was phosphorylated by PKC. These data suggest that calmodulin may be an inhibitor of GRK2 whose effects can be abolished with PKC-mediated phosphorylation of GRK2...
  66. ncbi request reprint Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits
    U Quitterer
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, 97078 Wurzburg, Germany
    J Biol Chem 276:6763-9. 2001
    ..Thus, the paradoxical block of PTH release under magnesium deficiency seems to be mediated through a novel mechanism involving an increase in the activity of G alpha subunits of heterotrimeric G-proteins...
  67. ncbi request reprint Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes
    Marc Brede
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, 97078 Wurzburg, Germany
    Mol Endocrinol 17:1640-6. 2003
    ..Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation...
  68. ncbi request reprint Measurement of the millisecond activation switch of G protein-coupled receptors in living cells
    Jean Pierre Vilardaga
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str 9, D 97078 Wurzburg, Germany
    Nat Biotechnol 21:807-12. 2003
    ..This approach allows the comparison of agonist and partial agonist intrinsic activities at the receptor level and provides evidence for millisecond activation times of GPCRs...
  69. pmc Persistent cAMP-signals triggered by internalized G-protein-coupled receptors
    Davide Calebiro
    Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    PLoS Biol 7:e1000172. 2009
    ..These data suggest that classical paradigms of GPCR signaling may need revision, as they indicate that cAMP signaling by GPCRs may occur both at the cell surface and from intracellular sites, but with different consequences for the cell...
  70. doi request reprint Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction
    Geertje Lewin
    Institute of Pharmacology and Toxicology, University of Munster, Munster, Germany
    Circulation 119:79-88. 2009
    ....
  71. doi request reprint Pathological autoantibodies in cardiomyopathy
    Roland Jahns
    Department of Internal Medicine, Medizinische Klinik und Poliklinik I, Cardiology, University of Wurzburg, Wurzburg, Germany
    Autoimmunity 41:454-61. 2008
    ..The following article will summarize the so far available evidence for an implication of a confined number of harmful autoantibodies directed against specific cardiac antigens in the pathogenesis of DCM...
  72. ncbi request reprint Fluorescent sensors for rapid monitoring of intracellular cGMP
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology, Versbacher Str 9, D 97078 Wurzburg, Germany
    Nat Methods 3:23-5. 2006
    ..The temporal and spatial resolution attained with the new sensors is superior to that of existing techniques, and permits direct recording and imaging of rapid cGMP-signaling events...
  73. ncbi request reprint The amino-terminal domain of G-protein-coupled receptor kinase 2 is a regulatory Gbeta gamma binding site
    Tanja Eichmann
    Institut fur Pharmakologie und Toxikologie, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 278:8052-7. 2003
    ..Thus, the amino-terminal domain of GRK2 is a previously unrecognized Gbetagamma binding site that regulates GRK2-mediated receptor phosphorylation and inhibits Gbetagamma-stimulated signaling...
  74. pmc Dynamics of receptor/G protein coupling in living cells
    Peter Hein
    Department of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany
    EMBO J 24:4106-14. 2005
    ..Our data suggest that alpha(2A)-adrenergic receptors and G proteins interact by rapid collision coupling and indicate that there is no significant precoupling between these receptors and G proteins...
  75. ncbi request reprint Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits
    Leif G Hommers
    University of Wurzburg, Department of Pharmacology and Toxicology, Versbacherstrasse 9, Germany
    J Biol Chem 278:1037-43. 2003
    ....
  76. doi request reprint Cardiac beta1-adrenoceptor autoantibodies in human heart disease: rationale and design of the Etiology, Titre-Course, and Survival (ETiCS) Study
    Nikolas Deubner
    Department of Internal Medicine I, Centre of Cardiovascular Medicine, University of Wurzburg, University Hospital Wurzburg, Klinikstrasse 6 8, 97070 Wurzburg, Germany
    Eur J Heart Fail 12:753-62. 2010
    ....
  77. pmc Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism
    Marian Castro
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    Proc Natl Acad Sci U S A 102:16084-9. 2005
    ..These data suggest that the conformational change that switches the receptor into its active state proceeds in a sequential manner, with the first rapid binding step event preceding receptor activation by PTH(1-34)...
  78. ncbi request reprint Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins
    Marian Castro
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, Germany
    Endocrinology 143:3854-65. 2002
    ..A major role for PKC and beta-arrestins in preferential regulation of PTHR-mediated G(q) signaling by independent mechanisms at the receptor level was established...
  79. doi request reprint Antibodies to cardiac receptors
    V Boivin-Jahns
    Comprehensive Heart Failure Center, University Hospital Wurzburg, DFG Forschungszentrum für Biomedizin, University of Wurzburg, Straubmühlweg 2a, 97078, Wurzburg, Germany
    Herz 37:843-8. 2012
    ....
  80. ncbi request reprint Immunofluorescent imaging of beta 1- and beta 2-adrenergic receptors in rat kidney
    V Boivin
    Institute of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg, Germany
    Kidney Int 59:515-31. 2001
    ....
  81. ncbi request reprint Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2
    Kristina Lorenz
    Institut fur Pharmakologie und Toxikologie, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    Nature 426:574-9. 2003
    ..A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity...
  82. doi request reprint Site-specific, orthogonal labeling of proteins in intact cells with two small biarsenical fluorophores
    Alexander Zürn
    Institute of Pharmacology and Toxicology, Rudolf Virchow Center University of Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Bioconjug Chem 21:853-9. 2010
    ..We propose that this method may be widely applied to label intracellular proteins and to study their interactions in intact cells with minimal disturbance of their function...
  83. pmc Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor
    Christoph Klenk
    Institute of Pharmacology and Toxicology, University of Wurzburg, 97078 Wurzburg, Germany
    J Biol Chem 285:30355-62. 2010
    ..These findings suggest a model in which NHERF1 may serve as an adaptor, bringing β-arrestin2 into close proximity to the PTHR, thereby facilitating β-arrestin2 recruitment after receptor activation...
  84. ncbi request reprint Mutation of Asn293 to Asp in transmembrane helix VI abolishes agonist-induced but not constitutive activity of the beta(2)-adrenergic receptor
    Annette Hannawacker
    Institute of Pharmacology, University of Wurzburg, Wurzburg, Germany
    Mol Pharmacol 62:1431-7. 2002
    ..Furthermore, they indicate that Asn293 is a key residue in transferring conformational information from the agonist-binding site to the intracellular surface...
  85. ncbi request reprint Molecular mechanisms of receptor activation: real-time analysis by fluorescence resonance energy transfer
    Martin J Lohse
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str 9, D 97078 Wurzburg, Germany
    Auton Autacoid Pharmacol 23:231-3. 2003
  86. ncbi request reprint Peptide inhibitors of G protein-coupled receptor kinases
    Rainer Winstel
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str 9, 97078 Wurzburg, Germany
    Biochem Pharmacol 70:1001-8. 2005
    ..These findings demonstrate that specific peptides can inhibit GRKs in the submicromolar range and suggest that a further decrease in size is possible without losing the inhibitory potency...
  87. ncbi request reprint The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy
    Monika Buitrago
    Rudolf Virchow Center DFG Research Center for Experimental Biomedicine, University of Wuerzburg, Versbacher Strasse 9, 97078 Wuerzburg, Germany
    Nat Med 11:837-44. 2005
    ..These findings implicate the Nab1-Egr1 axis as a crucial regulator of pathological cardiac growth...
  88. doi request reprint Real-time monitoring of phosphodiesterase inhibition in intact cells
    Sabine Herget
    Institute of Pharmacology and Toxicology, University of Wurzburg, 97078 Wurzburg, Germany
    Cell Signal 20:1423-31. 2008
    ..It allows to sense cAMP gradients around particular PDE molecules and to study the pharmacological effects of selective inhibitors on localized cAMP signalling...
  89. ncbi request reprint Real-time monitoring of the PDE2 activity of live cells: hormone-stimulated cAMP hydrolysis is faster than hormone-stimulated cAMP synthesis
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 280:1716-9. 2005
    ....
  90. pmc Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice
    S Engelhardt
    Institut fur Pharmakologie, Universitat Wurzburg, Versbacher Strasse 9, 97078 Wurzburg, Germany
    Proc Natl Acad Sci U S A 96:7059-64. 1999
    ..We conclude that overexpression of beta1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased beta1-adrenergic receptor signalling is ultimately detrimental...
  91. ncbi request reprint Inhibition of Na(+)-H(+) exchange prevents hypertrophy, fibrosis, and heart failure in beta(1)-adrenergic receptor transgenic mice
    Stefan Engelhardt
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, Germany
    Circ Res 90:814-9. 2002
    ..We conclude that the cardiac Na(+)-H(+) exchanger 1 is essential for the detrimental cardiac effects of chronic beta(1)-receptor stimulation in the heart...
  92. pmc cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes
    Sunita Warrier
    Department of Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4970, USA
    J Physiol 580:765-76. 2007
    ....
  93. ncbi request reprint G protein-coupled receptors: too many dimers?
    Martin J Lohse
    Nat Methods 3:972-3. 2006
  94. ncbi request reprint Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists
    Uwe Kirchhefer
    Institut fur Pharmakologie und Toxikologie, Westfalische Wilhelms Universitat, Domagkstr 12, 48149 Munster, Germany
    Cardiovasc Res 62:122-34. 2004
    ..Moreover, triadin 1 appears to anchor calsequestrin to the ryanodine receptor...
  95. ncbi request reprint Modulation of a brain voltage-gated K+ channel by syntaxin 1A requires the physical interaction of Gbetagamma with the channel
    Izhak Michaelevski
    Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Ramat Aviv, Israel
    J Biol Chem 277:34909-17. 2002
    ..Taken together, we suggest a mechanism whereby syntaxin and G protein betagamma subunits interact concomitantly with a Kv channel to regulate its inactivation...
  96. ncbi request reprint Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases
    Marco Mongillo
    Dulbecco Telethon Institute, Padova, Italy
    Circ Res 95:67-75. 2004
    ..PDE3 and PDE4 localize to distinct compartments and this may underpin their different functional roles. Our findings indicate the importance of distinctly localized PDE isoenzymes in determining compartmentalized cAMP signaling...
  97. pmc Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function
    Joachim P Schmitt
    Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:14525-30. 2006
    ..These results suggest that the depressed molecular function in cardiac myosin may initiate the events that cause the heart to remodel and become pathologically dilated...
  98. ncbi request reprint A role for caspase-1 in heart failure
    Sabine Merkle
    Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, Wuerzburg, Germany
    Circ Res 100:645-53. 2007
    ..Our findings support a functional role for caspase-1-mediated myocardial apoptosis contributing to the progression of heart failure...
  99. ncbi request reprint Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic receptor and Gi-protein heterotrimer
    Viacheslav O Nikolaev
    Institute of Pharmacology and Toxicology, University of Wurzburg, D 97078, Wurzburg, Germany
    J Biol Chem 281:24506-11. 2006
    ..The data provide a new key characteristic underlying the mechanism of partial agonism at G-protein-coupled receptors...
  100. ncbi request reprint Feedback inhibition of catecholamine release by two different alpha2-adrenoceptor subtypes prevents progression of heart failure
    Marc Brede
    Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, Germany
    Circulation 106:2491-6. 2002
    ..In addition, we determined the functional consequences of genetic variants of alpha2-adrenoceptors in human patients with chronic heart failure...
  101. ncbi request reprint Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy
    Martin Eigenthaler
    Institut für Klinische Biochemie und Pathobiochemie, Universitat Wurzburg, Germany
    Am J Physiol Heart Circ Physiol 285:H2471-81. 2003
    ..The results demonstrate that Ena-VASP proteins may play an important role in intercalated disk function at the interface between cardiac myocytes...