Agonist-dependent difference in the mechanisms involved in Ca2+ sensitization of smooth muscle of porcine coronary artery

被引:14
|
作者
Sato, A [1 ]
Hattori, Y
Sasaki, M
Tomita, F
Kohya, T
Kitabatake, A
Kanno, H
机构
[1] Hokkaido Univ, Sch Med, Dept Pharmacol, Sapporo, Hokkaido 0608638, Japan
[2] Hokkaido Univ, Sch Med, Dept Cardiovasc Med, Sapporo, Hokkaido 0608638, Japan
关键词
carbachol; endothelin-1; Ca2+ sensitization; Rho p21 protein; protein kinase C; tyrosine phosphorylation; vascular smooth muscle;
D O I
10.1097/00005344-200005000-00020
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study was undertaken to explore possible signal-transduction mechanisms involved in the Ca2+-sensitizing effects of carbachol and endothelin-l (ET-I) by using beta-escin-skinned smooth muscle of porcine coronary artery. Pretreatment with C3 exoenzyme of Clostridium botulinum, which selectively inactivates rho p21 by adenosine diphosphate (ADP) ribosylation, resulted in a significant inhibition of ET-1-induced Ca2+ sensitization, but had no effect on carbachol-induced Ca2+ sensitization. Whereas the protein kinase C (PKC inhibitors calphostin C and staurosporine did not affect the Ca2+-sensitizing effect of carbachol, the tyrosine kinase inhibitors genistein and tyrphostin 25 greatly but incompletely suppressed it. In contrast, the Ca2+-sensitizing effect of ET-1 was significantly inhibited by either calphostin C or genistein. Although the inhibitory effect of calphostin C on ET-1-induced Ca2+ sensitization was less than that of genistein, the effects of calphostin C and genistein were additive. The genistein-sensitive component of ET-1-induced Ca2+ sensitization appeared to include the C3-sensitive one. However, a substantial enhancement by ET-I of the Ca2+-induced contraction was observed even in the presence of the two inhibitors. In beta-escin-skinned smooth muscle of rabbit mesenteric artery, ET-1-induced Ca2+ sensitization was marginally affected by C3 pretreatment, calphostin C, and genistein. We conclude that, although PKC activation and rho p21 protein-dependent and -independent tyrosine phosphorylation each plays an important role in an increase in myofilament Ca2+ sensitivity, the contributions of these signaling pathways to Ca2+ sensitization are different depending on receptor agonists and tissues used. Furthermore, these data suggest the existence of an as yet undefined signal-transduction mechanism involved in Ca2+ sensitization caused by receptor agonists.
引用
收藏
页码:814 / 821
页数:8
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