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)
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Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
Arilla
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D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology*
D017481:Receptors, Somatostatin; C017426:somatostatin, iodine-Tyr-; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D013004:Somatostatin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D013331:Strychnine