Muscarinic stimulation of phosphatidylinositol metabolism in atria.
Phosphatidylinositol (PtdIns) turnover in murine atria is stimulated by the cholinergic agonist carbachol. Incorporation of either [32P]phosphate or [myo-3H]inositol into PtdIns is increased 40-80% by 30 microM carbachol, but carbachol does not increase the labeling of other major phospholipids. Cholinergic stimulation of PtdIns synthesis is blocked by the muscarinic antagonist atropine. When Ca2+ is removed from the extracellular medium, there is a large increase in basal PtdIns synthesis, and carbachol does not produce any further increase in [32P]phosphate incorporation. Carbachol also stimulates hydrolysis of phosphoinositides as measured by myo[3H]inositol 1-phosphate accumulation. A maximal concentration of carbachol causes a 300-400% increase in phosphoinositide breakdown, and half-maximal stimulation occurs at a carbachol concentration of approximately 10 microM. Muscarinic stimulation of inositol phospholipid hydrolysis is seen in left and right atria as well as in ventricular tissue. The effect of carbachol on phosphoinositide hydrolysis is markedly attenuated when extracellular Ca2+ is removed. In contrast to most other hormone receptors linked to PtdIns metabolism, there is no evidence that cardiac muscarinic receptors mediate their physiological effects through Ca2+ mobilization. Thus, receptor-mediated changes in PtdIns turnover may serve a different function in the heart than in hormone-receptor systems that utilize Ca2+ as a second messenger.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D006325:Heart Atria / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D014403:Tubocurarine / Q000494:pharmacology
D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D007294:Inositol; D001285:Atropine; D002217:Carbachol; D002118:Calcium; D014403:Tubocurarine