Product inhibition of the actomyosin subfragment-1 ATPase in skeletal, cardiac, and smooth muscle.
We studied product inhibition of the actin-activated ATPase of myosin subfragment-1 (S-1) from the three types of muscle tissue: skeletal, cardiac, and smooth. Increasing levels of [MgADP] in the 0-1-mM range caused significant inhibition of the actin-activated MgATPase activity of cardiac and gizzard but not skeletal muscle S-1. When total nucleotide concentration ([ATP] + [ADP]) was kept constant at 1 mM, ATPase activity was inhibited by 50% at an ADP/ATP ratio of 6:1 for cardiac S-1 and 3:1 for gizzard S-1. For skeletal S-1, however, even a 19:1 ratio did not cause 50% inhibition of ATPase activity. The observed effect was not due to changes in pH or inorganic phosphate concentration, nor could it be explained by substrate (ATP) depletion. In the absence of actin, ADP had little or no inhibitory effect on the ATPase activity of S-1, and these observations imply that ADP is competing directly for the ATP binding site of the actin-S1 complexes of cardiac and smooth muscle S-1. ADP has previously been shown to be a weak competitive inhibitor of the ATPase activity in skeletal muscle. The current data imply that ADP is a very effective competitive inhibitor for the actin-activated ATPase activity of cardiac and gizzard S-1 and, therefore, that ADP may be a physiologically important modulator of contractile activity in cardiac and smooth muscle.
Drew
J S
JS
Department of Medicine, State University of New York, Stony Brook 11794-8171.
Harwalkar
V A
VA
Stein
L A
LA
D000199:Actins / Q000494:pharmacology; D000205:Actomyosin / Q000037:antagonists & inhibitors*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000070559:Gizzard, Non-avian / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000201:enzymology; D009132:Muscles / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D010758:Phosphorus / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D000199:Actins; D009124:Muscle Proteins; D010446:Peptide Fragments; D010758:Phosphorus; D000244:Adenosine Diphosphate; D000205:Actomyosin; D000251:Adenosine Triphosphatases