Regulatory mechanisms of calponin phosphorylation in endothelin-1-induced contraction of porcine coronary artery.
Calponin is an actin-associated protein that appears to play an auxiliary regulatory role in the contraction of smooth muscle. We report here on the mechanisms for regulation of calponin phosphorylation in the endothelin-1-induced contraction of porcine coronary artery. Treatment of strips of porcine artery with endothelin-1 increased calponin phosphorylation and contraction in a concentration-dependent manner. The time course of the phosphorylation was biphasic, with the response to endothelin-1. The extent of phosphorylation reached a maximum within 5 min of stimulation with 10(-7)M endothelin-1 and then it declined rapidly to reach a minimum at 20 min. A potent inhibitor of protein kinase C, GF109203X, inhibited both calponin phosphorylation and contraction that were induced by endothelin-1 at 5 min, without an inhibition for myosin light chain phosphorylation. Protein phosphatase inhibitor, okadaic acid, had no effect on the extent of phosphorylation at 5 min, but it significantly inhibited the subsequent decrease in calponin phosphorylation. In contrast, in PDBu-treated strips of coronary artery, okadaic acid caused a significant steady increase of the extent of calponin phosphorylation. Our results suggest that calponin phosphorylation might be regulated by protein kinase C and okadaic acid sensitive protein phosphatases, in the endothelin-1-induced contraction of porcine coronary artery.
Yuasa
U
U
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan.
Mino
T
T
Naka
M
M
Yada
I
I
Tanaka
T
T
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008840:Microfilament Proteins; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D000096985:Calponins
D002135:Calcium-Binding Proteins; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D008840:Microfilament Proteins; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases; D000096985:Calponins; C070515:bisindolylmaleimide I