Somatostatin receptor-GTP binding regulatory protein-adenylyl cyclase system in hippocampal membranes of strychnine-treated rats.

Wistar rats were injected with either a non-convulsive dose (37.5 micrograms/100 g body weight (b.wt.), intravenously (i.v.)) or a convulsive dose (50 or 80 micrograms/100 g b.w.t, i.v.) of strychnine. Binding of 125I-Tyr11-somatostatin (125I-Tyr11-SS) to its specific receptors was measured in hippocampal membranes 15 min after strychnine injection at these three doses. The non-convulsive dose of strychnine did not affect binding of SS in the hippocampus whereas both convulsive doses decreased the number of specific SS receptors without influencing their apparent affinity. Somatostatin-like immunoreactivity (SSLI), SS-modulated adenylyl cyclase (AC) activity and the inhibitory guanine-nucleotide binding regulatory protein were also measured in rats treated with 80 micrograms/100 g b.wt. of strychnine. SSLI content remained stable. No significant differences were seen for the basal and forskolin (FK)-stimulated AC enzyme activities in the hippocampus of strychnine-treated rats when compared to the control group. The capacity of SS to inhibit basal and FK-stimulated AC activity in the hippocampus was significantly lower in the strychnine group than in the control group. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate [Gpp(NH)p] to inhibit FK-stimulated AC activity was also decreased in hippocampal membranes from strychnine-treated rats. These results suggest that the attenuated inhibition of AC by SS in hippocampal membranes from strychnine-treated rats may be caused by decreases in both Gi activity and in the number of SS receptors.(ABSTRACT TRUNCATED AT 250 WORDS)