Full and Partial Agoists Induce Distinct Desensitized States of the 5-HT₃ Receptor

Abstract

5-HT, receptor-mediated ion currents evoked by the full agonists 5-hydroxy-tryptamine (5-HT), quatemary 5-HT (5-HTQ), meta-chlorophenylbiguanide (mCPBG) and the partial agonists dopamine and tryptamine have been investigated in whole-cell voltage clamp experiments on N1E-115 mouse neuroblastoma cells. All agonists desensitize the 5-HT₃ receptor completely with a steep concentration dependence and a potency order of: mCPBG > 5-HTQ = 5-HT >> tryptamine > dopamine. The time course of recovery from desensitization depends on the agonist used. Recovery from partial agonist-induced desensitization is single exponential. whereas the desensitization induced by full agonists recovers with sigmoid kinetics, suggesting at least 3 transitions between 4 states. It is concluded that full and partial agonists induce distinct desensitized states.