Full and partial agonists induce distinct desensitized states of the 5-HT3 receptor.
5-HT3 receptor-mediated ion currents evoked by the full agonists 5-hydroxy-tryptamine (5-HT), quaternary 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 approximately 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.
van Hooft
J A
JA
Research Institute of Toxicology, Utrecht University, The Netherlands.
Vijverberg
H P
HP
D000818:Animals; D001645:Biguanides / Q000378:metabolism; D005071:Evoked Potentials; D051379:Mice; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001645:Biguanides; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D019789:Tetraethylammonium; C065734:1-(3-chlorophenyl)biguanide