Adenylate cyclase of Torpedo synaptosomes is inhibited by calcium and not affected by muscarinic ligands.
Cholinergic synaptosomes isolated from the electric organ of Torpedo contain membrane-bound adenylate cyclase activity (approximately 6 pmol/mg protein/min), which is dependent on the presence of guanine nucleotides. The activity is strongly dependent on temperature and only slightly affected by NaCl. The Torpedo adenylate cyclase is completely inhibited by low levels of free Ca2+ (KD approximately 0.5 microM). This effect is not altered by either trifluoperazine or addition of exogenous calmodulin. Ca2+ has no effect on the activation step of the adenylate cyclase by guanyl-5'-yl imidodiphosphate (GppNHp), and Mn2+ abolishes the Ca2+-dependent inhibition of cyclic AMP synthesis. These findings suggest that Ca2+ exerts its effect by direct interaction with a site located on the catalytic subunit. Torpedo synaptosomes contain presynaptic inhibitory muscarinic receptors. The binding of muscarinic agonists to the receptors is modulated (to lower affinity) by GTP. However, muscarinic ligands, examined under a variety of assay conditions, have no effect on adenylate cyclase activity. These results suggest that although both the muscarinic receptor and the adenylate cyclase are coupled to G proteins, they either interact with different G proteins or are situated in different regions of the presynaptic membrane.
D000109:Acetylcholine / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology; D004557:Electric Organ / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013574:Synaptosomes / Q000201:enzymology*; D014101:Torpedo; D014268:Trifluoperazine / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D014268:Trifluoperazine; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000109:Acetylcholine; D002118:Calcium