Agonist and inverse agonist efficacy at human recombinant serotonin 5-HT1A receptors as a function of receptor:G-protein stoichiometry

摘要: Abstract Membrane preparations were made from Chinese Hamster Ovary (CHO) cells expressing 1.6 and 4.2 pmol/mg of recombinant human 5-HT 1A receptors, as determined by saturation binding with the selective antagonist, [ 3 H]-S 15535 ([ H]-4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine). There was no change in number G-proteins activated full agonist, serotonin (5-HT; approximately 1.1 each preparation, measured 35 S]-GTPγS binding), therefore increasing receptor:G-protein ratio ≈1.4:1 (RG low ) to ≈4:1 high ). Agonist efficacy stimulation binding. The serotonergic eltoprazine, behaved a partial agonist ( E max = 52.7%) at RG membranes but virtually 93.2%) membranes, relative (= 100%). latter exhibited two-fold shift left its concentration-response curve compared P N -{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- -(2-pyridinyl)- cyclo-hexane-carboxamide), did not alter basal levels either membrane preparation. In contrast, spiperone displayed inverse activity, decreasing 17% 28% membranes. These data indicate that an increased (i) augments potency agonists, (ii) increases agonists (iii) negative receptors. Furthermore, these suggest induces, or stabilises, G-protein-coupled, inactive conformation receptor. © 1997 Elsevier Science Ltd.