M2-specific muscarinic cholinergic receptor-mediated inhibition of cardiac regulatory protein phosphorylation.
Acetylcholine acting via muscarinic cholinoceptors decreased phosphorylation of phospholamban and troponin I without reducing adenosine 3',5'-cyclic monophosphate (cAMP) levels or cAMP-dependent protein kinase activity ratio in the presence of 10-100 nM isoproterenol in guinea pig ventricular myocytes. The effect of acetylcholine was more pronounced when adenosine deaminase (5 U/ml) was present and incubation period was short (10 s). Okadaic acid, an inhibitor of protein phosphatase activity, blocked the acetylcholine-mediated inhibition of isoproterenol-stimulated phosphorylation of phospholamban. It is suggested that acetylcholine reduces protein phosphorylation by a cAMP-independent mechanism in guinea pig ventricular myocytes.
Gupta
R C
RC
Henry Ford Hospital, Detroit, Michigan 48202.
Neumann
J
J
Boknik
P
P
Watanabe
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D019319:Okadaic Acid; D010277:Parasympathomimetics / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000502:physiology*; D014336:Troponin / Q000378:metabolism*; D019210:Troponin I; D000099211:Phospholamban
D000109:Acetylcholine; D002135:Calcium-Binding Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D004988:Ethers, Cyclic; D009712:Nucleotides, Cyclic; D019319:Okadaic Acid; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D014336:Troponin; D019210:Troponin I; D000099211:Phospholamban