Adenosine and 5'-chloro-5'-deoxyadenosine inhibit the phosphorylation of phosphatidylinositol and myosin light chain in calf aorta smooth muscle.
Smooth muscle from calf aorta is homogenized and centrifuged. The insoluble material is subjected to sucrose density gradient centrifugation. When the heaviest fraction so obtained is incubated with radioactive ATP, two components incorporate most of the acid-insoluble radioactivity. One is a phosphoprotein with a molecular weight of 21,000. It has been identified as myosin light chain by its molecular weight, isoelectric point, and precipitation by antibody to calf aorta myosin. Its phosphorylation is strongly inhibited by EGTA, in agreement with published reports that myosin light chain kinase of smooth muscle is Ca2+ dependent. The other product is of low molecular weight, is extracted into acidic chloroform-methanol, and has been identified as phosphatidylinositol 4-phosphate. Adenosine and 5'-chloro-5'-deoxyadenosine, which are vasodilators, inhibit the phosphorylation of both substrates. Phosphorylation of phosphatidylinositol is inhibited at lower concentrations of the nucleosides than is the phosphorylation of myosin light chain. The inhibitory effects of the two nucleosides are not associated with changes in the concentration of cyclic AMP. The precise function of phosphatidylinositol phosphorylation in smooth muscle is not known, but correlations between smooth muscle contraction and increased turnover of phosphatidylinositol and its mono- and diphosphates have been reported. Myosin light chain is phosphorylated under conditions which favor smooth muscle contraction. We conclude that the inhibitory effects of adenosine described here are consistent with their physiological action as vasodilators.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002852:Chromatography, Ion Exchange; D017338:Cladribine; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D013997:Time Factors
D003839:Deoxyadenosines; D010716:Phosphatidylinositols; D017338:Cladribine; D004533:Egtazic Acid; C044739:5'-chloro-5'-deoxyadenosine; D009218:Myosins; D000241:Adenosine