GR127935 acts as a partial agonist at recombinant human 5-HT1D alpha and 5-HT1D beta receptors

European Journal of Pharmacology
J M WatsonD N Middlemiss

Abstract

In this study we have investigated the functional activity of GR127935 (2-methyl-1,2,4 oxadiazol-3-yl)-biphenyl-[4-carboxylic acid 4-methoxy-3-(4-methyl-piperazine-1-yl]-amide) at human 5-HT1D alpha and 5-HT1D beta receptors which have been expressed in a Chinese Hamster Ovary (CHO) cell line. Using [35S] GTP gamma S binding to cell membranes as a measure of receptor-G protein coupling. GR127935 showed partial agonist activity in both 5-HT1D alpha and 5-HT1D beta receptor expressing cells (Emax: 29 and 31% above basal control; pEC50: 8.6 and 9.7, respectively). GR127935 also acted as a potent antagonist at the 5-HT1D alpha (app. pA2 8.5) and 5-HT1D beta (app. pA2 9.1) receptors. From studies measuring cAMP accumulation in cultured CHO cells GR127935 also displayed partial agonism, as well as acting as a potent antagonist at the 5-HT1D alpha receptors which stimulate cAMP levels and 5-HT1D beta receptors which inhibit cAMP levels (app. pA2 8.6 and 9.7, respectively). The 5\-HT1-like receptor antagonist methiothepin showed negative intrinsic activity at both receptors in the [35S]GTP gamma S binding assay only. From studies using the receptor alkylating agent EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) the 5-HT1D alpha ...Continue Reading

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R L WeinshankP R Hartig
Nov 14, 1991·Biochemical and Biophysical Research Communications·C MaenhautJ E Dumont
Apr 1, 1989·Trends in Pharmacological Sciences·D Hoyer, D N Middlemiss
Jun 1, 1989·Clinical and Experimental Pharmacology & Physiology·A D Crocker, D L Cameron
Jul 7, 1988·European Journal of Pharmacology·R BouhelalJ Bockaert
Oct 15, 1993·European Journal of Pharmacology·J Van SandeC Maenhaut
Dec 4, 1995·European Journal of Pharmacology·D M WalshH E Connor
Jan 1, 1996·British Journal of Pharmacology·C RobertsB J Jones
Jan 1, 1995·Journal of Psychopharmacology·J P HatcherJ J Hagan

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Citations

Dec 4, 1995·European Journal of Pharmacology·D M WalshH E Connor
Jan 1, 1996·Behavioural Brain Research·G W PriceB J Jones
Mar 10, 2001·European Journal of Pharmacology·S E O'ConnorP Janiak
Jul 23, 1997·European Journal of Pharmacology·J J HaganD N Middlemiss
May 7, 1998·European Journal of Pharmacology·H O KalkmanM D Tricklebank
Aug 12, 1999·European Journal of Pharmacology·D N MiddlemissG W Price
Jun 6, 2000·Pharmacology, Biochemistry, and Behavior·D M Tomkins, M F O'Neill
Mar 28, 2002·Pharmacology & Therapeutics·J R RaymondM N Garnovskaya
Jun 1, 1997·British Journal of Pharmacology·C DavidsonJ A Stamford
Oct 17, 1998·British Journal of Pharmacology·J V SelkirkG W Price
Jan 12, 1999·British Journal of Pharmacology·J WatsonA M Brown
May 12, 2000·British Journal of Pharmacology·D R ThomasG W Price
Jul 17, 2001·British Journal of Pharmacology·J WatsonD N Middlemiss
May 23, 2014·Pharmacology, Biochemistry, and Behavior·Dane AronsenSusan Schenk
Mar 31, 2006·European Journal of Pharmacology·Claire ScottJeannette Watson
Jul 13, 2000·Journal of Psychopharmacology·S HjorthS B Auerbach
Jan 10, 2019·Journal of Neurophysiology·Ana M Lucas-OsmaDavid J Bennett
Aug 10, 2011·The Journal of Pharmacology and Experimental Therapeutics·Minli ZhangM Edward Pierson
Feb 7, 2001·The Journal of Biological Chemistry·J K ChambersG P Livi
Feb 7, 2002·CNS Drug Reviews·C RobertsD N Middlemiss
May 13, 2005·Journal of Medicinal Chemistry·Simon E WardJeannette M Watson

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