Autonomic regulation of type 1 protein phosphatase in cardiac muscle.
Muscarinic cholinergic agonists such as acetylcholine attenuate phosphorylation of phospholamban induced by agents that activate cAMP-dependent protein kinase. However, cAMP accumulation is variably affected or only slightly reduced; thus, the choline ester might produce effects in addition to inhibition of adenylate cyclase. We hypothesized that acetylcholine might regulate a phosphatase in mammalina myocardium. Exposure of Langendoff-perfused guinea pig ventricles to isoproterenol (10 nM) for 45 s increased phosphatase inhibitor-1 activity 2-fold. Co-administration of acetylcholine (100 nM) antagonized the effect of isoproterenol, and atropine (1 microM) blocked the effect of acetylcholine. Forskolin (1 microM) caused a 3-fold increase in inhibitor-1 activity, and acetylcholine markedly attenuated the effect of forskolin. However, acetylcholine did not lower cAMP levels in the same tissues. Both isoproterenol and forskolin reduced the type 1 phosphatase activity intrinsic to sarcoplasmic reticulum by 25-50%, using [32P]phosphorylase a or 32P-labeled membrane vesicles as a substrate for the phosphatase. Co-administration of acetylcholine markedly attenuated these effects of isoproterenol and forskolin. Acetylcholine alone caused a 50% increase in type 1 phosphatase activity. We concluded that inhibitor-1 and type 1 phosphatase can be regulated in intact cardiac muscle by agents that increase intracellular cAMP and by acetylcholine.
Ahmad
Z
Z
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
Green
F J
FJ
Subuhi
H S
HS
Watanabe
A M
AM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D011976:Receptors, Muscarinic; D005576:Colforsin; D010749:Phosphoprotein Phosphatases; D007545:Isoproterenol; D000109:Acetylcholine