ACTIVATION OF PROTEIN-KINASE-C AS A MODULATOR OF POTENTIATED UK-14304-INDUCED CONTRACTIONS IN DOG MESENTERIC-ARTERY AND VEIN

被引：6

作者：

SHIMAMOTO, H ^{[1
]}

SHIMAMOTO, Y ^{[1
]}

KWAN, CY ^{[1
]}

DANIEL, EE ^{[1
]}

机构：

[1] MCMASTER UNIV,DEPT BIOMED SCI,DIV PHYSIOL & PHARMACOL,SMOOTH MUSCLE RES PROGRAM,HAMILTON,ON L8N 3Z5,CANADA

来源：

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY | 1995年 / 26卷 / 06期

关键词：

PROTEIN KINASE C; ALPHA-ADRENOCEPTORS; AMPLIFICATION-CALPHOSTIN C;

D O I：

10.1097/00005344-199512000-00011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We assessed the role of protein kinase C (PKC) in the mechanism responsible for the potentiation of UK-14304-induced contractions produced when isolated dog mesenteric vascular rings were pretreated with threshold concentrations of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), KCl, or endothelin-l (ET-1). In dog mesenteric artery. UK-14304 produced a biphasic concentration-response curve in the presence of TPA, KCL, or ET-1, with the curve portion at lower concentrations being alpha(2)-adrenoceptor dependent and the portion at higher concentrations being alpha(1)-adrenoceptor dependent. Calphostin C (10(-6)M), a PKC inhibitor, abolished amplified UK-14304-induced contraction in the TPA-pretreated tissues. In the KCl- and ET-l-pretreated tissues, 10(-6)M calphostin C antagonized amplified UK-14304-induced contractions by similar to 20% in both parts of the concentration-response curve. In contrast, in dog mesenteric vein, amplified UK-14304-induced contractions by TPA, KCl, and ET-1 were entirely dependent on alpha(2)-adrenoceptors. Calphostin C (10(-6)M), which in control experiments had no effect on KCl-induced contraction and antagonized responses to TPA by 60.1%, inhibited UK-14304-induced contraction by 18.3%. Amplified UK-14304-induced contraction was antagonized by 10(-6)M calphostin C by 21.8% in KCl-precontracted tissues, 58.1% in ET-l-precontracted tissues, and 66.3% in TPA-precontracted tissues. In the ET-1- and TPA-pretreated dog mesenteric veins, 10(-6)M calphostin C decreased maximal tensions of enhanced UK-14304-induced contractions to the same level as the UK-14304-induced maximal tension inhibited by 10(-6)M calphostin C in untreated dog mesenteric vein. Therefore, TPA can be a precontracting agent that amplifies UK-14304-induced contractions through PKC activation in both dog mesenteric artery and vein. PKC predominantly mediates the contraction amplification mechanisms after exposure to ET-1 in dog mesenteric vein and does not play a major role in the amplification of UK-14304-induced contraction by KCl in both dog mesenteric artery and vein, These data show that a common mechanism need not underlie amplification of adrenergic responses in mesenteric artery and vein.

引用

页码：923 / 931

页数：9

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