On the mechanism of muscarinic hydrolysis of choline phospholipids in the heart.
In the heart, choline phospholipids were by far the largest fraction (about 50%) of phospholipids, much larger than that of inositol phospholipids (less than 6%) and phosphatidic acid (0.3%). The choline phospholipids (11 mumol/g) maintained a constant efflux of choline of about 1.5 nmol g-1 min-1 into the perfusate. Carbachol (10 microM) rapidly enhanced the choline efflux by a muscarinic mechanism, that was independent of mepacrine, an inhibitor of phospholipase A2, as well as of extracellular Ca2+; the maximum acceleration was reached within 2 min. In contrast, the accumulation of inositol phosphates by carbachol was blocked in the presence of a Ca2+-free perfusion medium. Similar to the carbachol-evoked choline efflux, the increase in tissue content of phosphatidic acid by carbachol was unaffected by infusion of a Ca2+-free, EGTA-containing solution. Sodium oleate (20 microM), an activator of phospholipase D, imitated the effects of carbachol on choline and phosphatidic acid, whereas NaF (5 mM), which has been reported to inhibit phospholipase D, blocked carbachol-evoked efflux of choline. In conclusion, muscarinic receptor stimulation enhanced the hydrolysis of choline phospholipids presumably via activation of phospholipase D. The immediate formation of choline, phosphatidic acid and presumably diacylglycerol is discussed including its possible physiological importance.
Lindmar
R
R
Department of Pharmacology, University of Mainz, Federal Republic of Germany.
Löffelholz
K
K
Sandmann
J
J
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002645:Chickens; D002794:Choline / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D013997:Time Factors
D001286:Atropine Derivatives; D007295:Inositol Phosphates; D008563:Membrane Lipids; D009829:Oleic Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D011976:Receptors, Muscarinic; D019301:Oleic Acid; C006649:methylatropine; D002217:Carbachol; D010740:Phospholipases; D010739:Phospholipase D; D011796:Quinacrine; D002794:Choline