A comparison of muscarinic acetylcholine receptors coupled to phosphatidylinositol turnover and to adenylate cyclase in guinea-pig atria and ventricles.
The affinities of muscarinic acetylcholine receptor agonist and antagonist compounds have been measured in studies of adenylate cyclase inhibition and phosphatidylinositol turnover in guinea-pig atria and ventricles. The affinities of all compounds tested were similar in atrial and ventricular preparations. However, three antagonists, atropine, pirenzepine and gallamine had different affinities at receptors coupled to adenylate cyclase inhibition compared with those which stimulated turnover of phosphatidylinositols. The neuromuscular blocking agents gallamine and pancuronium, which demonstrate cardioselective acetylcholine receptor antagonist activity, were competitive antagonists at receptors coupled to both second messenger systems. However, their affinities measured in both systems were lower than expected from tissue-response studies. Therefore, the cardioselectivity of these compounds cannot be explained by a simple competitive interaction with receptors coupled to either adenylate cyclase inhibition or phosphatidylinositol turnover.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D006352:Heart Ventricles; D066298:In Vitro Techniques; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D009466:Neuromuscular Blocking Agents; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000262:Adenylyl Cyclases