SYNERGISTIC EFFECTS OF CYCLIC AMP-RELATED VASODILATORS AND THE PHOSPHATASE INHIBITOR OKADAIC ACID

The phosphatase inhibitor okadaic acid at 100 nM slowly but completely inhibited high K+-induced contraction in the rat aorta (t1/2 = 118.9 min). High K+-induced contraction was partially inhibited (to 37-65%) by 1 muM forskolin, 100 muM dibutyryl cyclic AMP, 100 nM atrial natriuretic peptide, 1 muM nitroglycerin, 10 nM sodium nitroprusside, 300 pM nicardipine or 100 nM verapamil. The rate of relaxation due to okadaic acid became faster when the contraction was partially inhibited by these compounds. Augmentation of the relaxation was greater with forskolin and dibutyryl cyclic AMP than with the other inhibitors. These results support the suggestion that okadaic acid inhibits phosphatase to augment the phosphorylation due to cyclic AMP-dependent kinase, resulting in smooth muscle relaxation.