Tyrosine phosphorylation increases Ca2+ sensitivity of vascular smooth muscle contraction.
In order to elucidate the role of tyrosine phosphorylation in vasoconstriction, we investigated the effects of inhibitors of tyrosine kinase (genistein, 30 microM) and phosphatase (sodium o-vanadate, 5 microM) on the contraction of aorta isolated from guinea pig. Genistein significantly inhibited norepinephrine-induced contraction, but it did not affect that induced by KCI. Thus, tyrosine phosphorylation may not be involved in the contractile response to KCI alone. The aortic contraction elicited by KCl was significantly augmented by sodium o-vanadate, which increased both the maximum force and pD2 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 Ca2+-induced contraction in the aortic strips depolarized with KCl, increasing both its maximum force and pD2 values. Neither basal 45Ca2+ uptake nor verapamil-sensitive 45Ca2+ 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 Ca2+ entry but through increased Ca2+ sensitivity of the intracellular contractile pathway.
Masui
H
H
Department of Public Health, Hyogo College of Medicine, Nishinomiya, Japan.
Wakabayashi
I
I
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D019833:Genistein / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D014443:Tyrosine / Q000502:physiology*; D014638:Vanadates / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002132:Calcium Radioisotopes; D014662:Vasoconstrictor Agents; D014638:Vanadates; D014443:Tyrosine; D011189:Potassium Chloride; D019833:Genistein; D002118:Calcium; D009638:Norepinephrine