Involvement of Calcium in Cyclic Nucleotide Metabolism in Human Vascular Smooth Muscle

Abstract

When cyclic nucleotide phosphodiesterase was purified from isolated smooth muscle layer of human aorta by DEAE-cellulose column chromatography, separated cyclic GMP phosphodiesterase activity was markedly stimulated in the presence of 10–20 µM of Ca²⁺ by a protein modulator which has similar physico-chemical properties to troponin C. Synthetic compound, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, which produced relaxations of arteries contracted by prostaglandin F_2α or KCl was found to inhibit selectively this Ca²⁺-dependent cyclic GMP phosphodiesterase. This compound produced inhibition of superprecipitation of myosin B system obtained form mouse skeletal muscle and also inhibited adenosine triphosphatase activity of myosin B. Our data suggest that calcium is involved through a protein modulator in cyclic nucleotide metabolism of vascular smooth muscle and that the calcium-dependent protein modulator probably participates in the regulation of contractile response of vascular smooth muscle by affecting actomyosin ATPase activity.