TY - JOUR
T1 - Protection with phencyclidine against inactivation of 5-HT2 receptors by sulfhydryl-modifying reagents
AU - Toshitaka, Nabeshima
AU - Kazuhiro, Ishikawa
AU - Kazumasa, Yamaguchi
AU - Hiroshi, Furukawa
AU - Tsutomu, Kameyama
PY - 1988/9/1
Y1 - 1988/9/1
N2 - 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 μM) caused a significant decrease in Bmax without changing Kd. PCP (10 μM) and ritanserin (1 μM) protected [3H]PCP and [3H]ketanserin binding sites from the decrease in the number induced by NEM (100 μM). 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.
AB - 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 μM) caused a significant decrease in Bmax without changing Kd. PCP (10 μM) and ritanserin (1 μM) protected [3H]PCP and [3H]ketanserin binding sites from the decrease in the number induced by NEM (100 μM). 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.
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U2 - 10.1016/0006-2952(88)90639-9
DO - 10.1016/0006-2952(88)90639-9
M3 - Article
C2 - 3135811
AN - SCOPUS:0023683076
SN - 0006-2952
VL - 37
SP - 3277
EP - 3283
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 17
ER -