PMID: 1329292Oct 1, 1992Paper

Reverse intrinsic activity of antagonists on G protein-coupled receptors

Trends in Pharmacological Sciences
W Schütz, Michael Freissmuth


Biological effects observed with an antagonist are usually interpreted as the result of its ability to block receptor activation produced by an endogenous agonist. In this Principles article, Wolfgang Schütz and Michael Freissmuth show how considerable evidence has now been accumulated for G protein-coupled receptors that antagonists not only bind to the receptor, but also induce a conformational change that favours uncoupling of the receptor from its G protein. The spontaneous activity of the unliganded receptor (i.e. the receptor not occupied by any ligand) is a well-established phenomenon in reconstituted systems with purified components. However, its physiological relevance needs to be verified in a more physiological environment before biological effect of antagonists can be primarily ascribed to negative intrinsic activity.


Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·Michael FreissmuthA D Strosberg
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T Costa, A Herz
Apr 1, 1984·Pflügers Archiv : European journal of physiology·M Soejima, A Noma
Jan 1, 1980·Annual Review of Biochemistry·E M Ross, A G Gilman
Jun 11, 1982·Science·C BraestrupE N Petersen
Mar 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·E BurgisserR J Lefkowitz


Feb 15, 2001·Biopolymers·K ChaturvediR D Howells
Feb 1, 1995·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·T GudermannG Schultz
Jan 1, 1993·Journal of Neural Transmission. General Section·C L Nilsson, E Eriksson
Jan 15, 1999·Molecular Neurobiology·Petrus J Pauwels, Thierry Wurch
Jun 1, 1993·Pharmacology & Therapeutics·M P Caulfield
Dec 1, 1993·Trends in Pharmacological Sciences·T P Kenakin
Nov 1, 1994·Trends in Pharmacological Sciences·T P Kenakin
Jan 1, 1995·Neurobiology of Aging·M H Bigham, M S Lidow
Jan 1, 1996·General Pharmacology·J F KlinkerR Seifert
Jul 15, 1994·European Journal of Pharmacology·K Götze, K H Jakobs
May 1, 1994·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·L RossiniP Rossini
Mar 22, 2002·European Journal of Pharmacology·Lucía VelascoB Cantabrana
May 23, 1998·European Journal of Pharmacology·A ChahdiY Landry
Jan 1, 1995·Trends in Pharmacological Sciences·G MilliganM Lee
May 1, 1995·Trends in Pharmacological Sciences·P H NederkoornG M Donné-Op den Kelder
May 19, 1998·Trends in Pharmacological Sciences·L A Selbie, S J Hill
Aug 1, 1998·Brain Research. Molecular Brain Research·R J PrimusD W Gallager
Aug 22, 2001·Progress in Neuro-psychopharmacology & Biological Psychiatry·C M BullockQ Y Zhou
Oct 23, 1998·Molecular and Cellular Endocrinology·R ErlichS B Guild
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·L ArvanitakisM C Gershengorn
Mar 30, 2002·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Joseph F Siebenaller, Deiadra J Garrett
Jun 1, 1997·British Journal of Pharmacology·D A Hall, P G Strange
Apr 16, 1999·British Journal of Pharmacology·L DaefflerY Landry
Aug 5, 1999·British Journal of Pharmacology·D R VarmaS Mulay
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·Martine J SmitHenk Timmerman
May 5, 1998·Fundamental & Clinical Pharmacology·A ChahdiY Landry
May 5, 2000·Fundamental & Clinical Pharmacology·L Daeffler, Y Landry
Sep 1, 1996·British Journal of Pharmacology·M A NogueraP D'Ocon
Oct 28, 1998·The Journal of Clinical Investigation·M C GershengornI Clark-Lewis
Jan 10, 2003·Circulation Journal : Official Journal of the Japanese Circulation Society·Atsushi YaoToshiyuki Takahashi
Jan 14, 2004·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shin-ichiro MiuraSadashiva S Karnik
Feb 13, 2001·Biochemical and Biophysical Research Communications·R StaudingerJ C Bandrés
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·M HoheneggerMichael Freissmuth
Aug 8, 2014·Journal of Molecular Modeling·Hans-Joachim WittmannAndrea Strasser
Jun 29, 1995·Biochemical Pharmacology·T P KenakinM Lutz
Jan 1, 1997·Journal of Receptor and Signal Transduction Research·A Scheer, S Cotecchia
Jan 1, 1995·Immunity·S C Jameson, M J Bevan
May 3, 2000·Medical Hypotheses·A MansillaR Argüero
Nov 1, 1996·Chest·B F DickeyR Barber
Jul 5, 2005·Expert Opinion on Investigational Drugs·F JenckJ L Moreau
Mar 14, 2014·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shin-ichiro Miura, Keijiro Saku
Feb 6, 2008·Chemical Biology & Drug Design·Saurabh SenGregory V Nikiforovich
Jan 1, 1997·Journal of Receptor and Signal Transduction Research·W SiegristA N Eberle
Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas RauThomas Eschenhagen
Sep 3, 1998·The Journal of Biological Chemistry·K Wenzel-SeifertR Seifert
Aug 19, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ali El-ArmoucheDavor Pavlovic
May 12, 2000·American Journal of Physiology. Renal Physiology·J A DurrM S Blankenship
Jan 5, 2002·Journal of Receptor and Signal Transduction Research·S Lazareno
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bent PostmaKok P M van Kessel
Dec 1, 2014·In Silico Pharmacology·Hans-Joachim WittmannAndrea Strasser
Apr 17, 1998·European Journal of Pharmacology·M C Michel, M Goepel
Dec 12, 2003·Journal of Medicinal Chemistry·Marinella GovoniRob Leurs

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