In rat hippocampus, somatostatin 14 and muscarinic receptor ligands modulate an adenylate cyclase belonging to a common domain of the receptor.
In hippocampal slices, somatostatin 14 and its stable analog L363 [cyclo(Phe-Pro-Phe-D-Trp-Lys-Thr)] fail to modify muscarinic signal transduction mediated by stimulation of phosphoinositide breakdown, whereas somatostatin 14 mimics oxotremorine in inhibiting adenylate cyclase activity of hippocampal membranes. The simultaneous addition of somatostatin 14 and oxotremorine elicits a nonadditive convergent inhibition of adenylate cyclase activity. Both L363 and oxotremorine nonadditively stimulate a high-affinity guanosine 5'-triphosphatase activity of hippocampal membranes. This stimulation could be operative in mediating the convergent inhibition of adenylate cyclase activity elicited by the binding of specific ligands to somatostatin and muscarinic recognition sites present in hippocampal membranes. Because L363 competitively displaces muscarinic agonists fand antagonists from their specific recognition sites, one might infer that the two recognition sites interact functionally; that is, somatostatin reduces the efficacy of oxotremorine and/or vice versa.
D000109:Acetylcholine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D006868:Hydrolysis; D010095:Oxotremorine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D005576:Colforsin; D013004:Somatostatin; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D020558:GTP Phosphohydrolases; D000109:Acetylcholine