Tyrosine phosphorylation increases Ca 2+ sensitivity of vascular smooth muscle contraction

Abstract

In order to elucidate the role of tyrosine phosphorylation in vasoconstriction, we investigated the effects of inhibitors of tyrosine kinase (genistein, 30 μM) and phosphatase (sodium o-vanadate, 5 μM) on the contraction of aorta isolated from guinea pig. Genistein significantly inhibited norepinephrine-induced contraction, but it did not affect that induced by KCl. Thus, tyrosine phosphorylation may not be involved in the contractile response to KCl alone. The aortic contraction elicited by KCl was significantly augmented by sodium o-vanadate, which increased both the maximum force and pD 2 values of KCl contraction. In the presence of verapamil, KCl-induced contraction was abolished even after pretreatment with sodium o-vanadate. Sodium o-vanadate also augmented Ca 2+-induced contraction in the aortic strips depolarized with KCl, increasing both its maximum force and pD 2 values. Neither basal 45Ca 2+ uptake nor verapamil-sensitive 45Ca 2+ uptake induced by KCl were affected by pretreatment with sodium o-vanadate. These results suggest that tyrosine phosphorylation is involved in the contraction of guinea-pig aorta not through transplasmalemmal Ca 2+ entry but through increased Ca 2+ sensitivity of the intracellular contractile pathway.