Control of smooth muscle actomyosin by phosphate and 5′AMP: Possible role in metabolic autoregulation

Abstract

Inorganic phosphate (Pi) inhibits ATPase activity and syneresis of myofibrils and myosin B from vertebrate smooth muscle. This effect is not due to binding of Ca ++ by Pi. Smooth muscle actomyosin is also inhibited by 5′AMP, but the effect is small except at high AMP concentrations. When Pi and 5′AMP are simultaneously present in vitro, the inhibition of ATPase activity is greater than the sum of the separate effects of the two metabolites, and increases as substrate concentration decreases. Concentrations of Pi, 5′AMP and ATP which simulate those in normally oxygenated smooth muscle tissue produce little inhibition in vitro, but concentrations typical of ischemic muscle can almost completely eliminate contraction-coupled ATP hydrolysis. Since smooth muscles contain creatine kinase and adenylate kinase, but possess little 5′AMP deaminase activity, Pi and AMP could serve as oxygen-linked feed-back controls of ATP utilization. The foregoing ideas are applied to a theoretical analysis of the mechanism by which pre-capillary sphincter smooth muscle adjusts capillary density in accordance with local tissue metabolism.