Muscarinic receptor regulation of NG108-15 adenylate cyclase: requirement for Na+ and GTP.
Cholinergic agonists inhibit the basal and PGE1-activated adenylate cyclase activity in membranes isolated from the mouse neuroblastoma x glioma hybrid cell NG108-15. Inhibition is observed with acetylcholine, acetyl-beta-methylcholine and carbachol and is blocked by two specific muscarinic antagonists, atropine and quinuclydinylbenzilate. Inhibition of basal and PGE1-activated activity is only partial. Carbachol-directed inhibition has an apparent Km of 6 microM in the presence or absence of PGE1. Both the guanine nucleotide GTP and the monovalent cation Na+ are required for this muscarinic inhibition of basal and PGE1-activated NG108-15 adenylate cyclase. The selectivity observed for monovalent cations (all chloride salts) in this process is Na+ congruent to Li+ greater than K+ greater than Choline+ with the ED50 for Na+ congruent 40 microM. Of the nucleotides tested, only IT (and not ATP, UTP or CTP) replaces GTP in this process. GTP at 10 microM represents a saturating nucleotide concentration. Opiate-directed inhibition of NG108-15 adenylate cyclase has recently been shown to exhibit a similar requirement for GTP and Na+ [Blume, A. J., Lichtshtein, D. and Boone, G. (1979) Proc. National Academy of Sciences, USA, in press]. The data presented here therefore support the hypothesis that the general transfer of inhibitory information from membrane receptors to adenylate cyclase involves both a Na+ and GTP-sensitive process.
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002414:Cations, Monovalent / Q000378:metabolism; D002460:Cell Line; D003650:Decamethonium Compounds / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006822:Hybrid Cells / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology*; D009711:Nucleotides / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D002414:Cations, Monovalent; D003650:Decamethonium Compounds; D006584:Hexamethonium Compounds; D009711:Nucleotides; D011458:Prostaglandins E; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D006160:Guanosine Triphosphate; D002217:Carbachol; D012964:Sodium; D000262:Adenylyl Cyclases; D000109:Acetylcholine