CELLULAR MECHANISM OF THROMBIN ON ENDOTHELIN-1 BIOSYNTHESIS AND RELEASE IN BOVINE ENDOTHELIAL-CELL

被引：83

作者：

EMORI, T ^{[1
]}

HIRATA, Y ^{[1
]}

IMAI, T ^{[1
]}

OHTA, K ^{[1
]}

KANNO, K ^{[1
]}

EGUCHI, S ^{[1
]}

MARUMO, F ^{[1
]}

机构：

[1] TOKYO MED & DENT UNIV,DEPT INTERNAL MED 2,DIV ENDOCRINE HYPERTENS,YUSHIMA 1-5-45,BUNKYO KU,TOKYO 113,JAPAN

来源：

BIOCHEMICAL PHARMACOLOGY | 1992年 / 44卷 / 12期

关键词：

D O I：

10.1016/0006-2952(92)90687-E

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We have studied the cellular mechanism responsible for induction of preproendothelin (preproET)-1 mRNA and release of ET-1 by thrombin in cultured bovine endothelial cells (ECs). Thrombin induced an immediate and dose-dependent formation of inositol-1,4,5-trisphosphate (IP3) with a concomitant increase in intracellular Ca2+ concentration ([Ca2)]i). The thrombin-induced ET-1 release was abolished either by a phospholipase C inhibitor, a protein kinase C (PKC) inhibitor, or an intracellular Ca2+-chelator, whereas a Ca2+-channel antagonist was ineffective. A selective thrombin inhibitor (argatroban) decreased IP3 formation and the increase in [Ca2+]i and ET-1 release stimulated by thrombin. Northern blot analysis revealed that thrombin-induced expression of preproET-1 mRNA was inhibited completely by a PKC inhibitor and partially by argatroban. These data suggest that thrombin is involved in the mechanism of preproET-1 mRNA expression and subsequent ET-1 release, possibly through activation PKC and mobilization of intracellular Ca2+ resulting from the receptor-mediated phosphoinositide breakdown in ECs.

引用

页码：2409 / 2411

页数：3

共 10 条

[1] THROMBIN AND HISTAMINE ACTIVATE PHOSPHOLIPASE-C IN HUMAN-ENDOTHELIAL CELLS VIA A PHORBOL ESTER-SENSITIVE PATHWAY [J].