Sensitization of adenylate cyclase by short-term activation of 5-HT1A receptors.
Long-term (18 h) activation of 5-HT1A receptors alters 5-HT1A receptor-G protein coupling and leads to heterologous sensitization of adenylate cyclase. In contrast, the effects of short-term (2 h) 5-HT1A receptor activation on subsequent adenylate cyclase activity have not been determined. The present study examined and characterized 5-HT1A receptor-induced heterologous sensitization following short-term activation in CHO-5-HT1A cells. Short-term activation of 5-HT1A receptors with full agonists, as well as the partial agonist, buspirone, markedly enhanced subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization was evident after 30 min treatment with 5HT and appeared to be near maximal following 2 h agonist treatment. Sensitization was characterized by a dose-dependent increase in forskolin-stimulated cyclic AMP accumulation and was prevented by WAY 100635 or by pertussis toxin treatment. The ability of the 5-HT1A agonists to induce heterologous sensitization was not significantly altered by agents shown previously to modulate 5-HT1A-mediated inhibition of cyclic AMP accumulation.
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, MCMP 1333, RHPH 224A, West Lafayette, IN 47907, USA.
Joshua G
JG
Lisinicchia
Val J
VJ
Watts
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D016466:CHO Cells; D000001:Calcimycin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013997:Time Factors; D014363:Tryptamines / Q000494:pharmacology
D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D010703:Phorbol Esters; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D014363:Tryptamines; D044282:Receptor, Serotonin, 5-HT1A; C089776:LY 293284; D005576:Colforsin; C119222:phorbol-12-myristate; D016718:Arachidonic Acid; D012701:Serotonin; D000001:Calcimycin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003513:Cycloheximide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; C088060:bisindolylmaleimide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002065:Buspirone; D007213:Indomethacin