Protection with phencyclidine against inactivation of 5-HT2 receptors by sulfhydryl-modifying reagents.
We investigated whether phencyclidine (PCP)-induced head-twitch was antagonized in rats by ritanserin, a selective serotonin2 (5-HT2) receptor antagonist, to confirm the involvement of 5-HT neurons in PCP action and to discover whether PCP could protect the binding sites of [3H]PCP and [3H]ketanserin from the inhibitory effect of protein-modifying reagents which affect sulfhydryl groups. PCP (7.5, 10 and 12.5 mg/kg, i.p.)-induced head-twitch was completely antagonized by ritanserin (1 mg/kg, s.c.). Scatchard plots of specific [3H]PCP and [3H]ketanserin binding showed that sulfhydryl-modifying reagent, N-ethylmaleimide (NEM, 100 microM) caused a significant decrease in Bmax without changing Kd. PCP (10 microM) and ritanserin (1 microM) protected [3H]PCP and [3H]ketanserin binding sites from the decrease in the number induced by NEM (100 microM). 5-HT protected [3H]5-HT binding sites from inactivation by NEM, but PCP and ritanserin did not show any effect. On the basis of the present findings, it is concluded that PCP can interact with 5-HT2 receptors directly or allosterically, and 5-HT2 receptors may locate at PCP binding sites in membranes.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005033:Ethylmaleimide / Q000037:antagonists & inhibitors; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin; D012701:Serotonin / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000037:antagonists & inhibitors*
D010880:Piperidines; D011985:Receptors, Serotonin; D013439:Sulfhydryl Reagents; D016713:Ritanserin; D012701:Serotonin; D007650:Ketanserin; D010622:Phencyclidine; D005033:Ethylmaleimide