Mechanism of non-capacitative Ca2(+) influx in response to bradykinin in vascular endothelial cells
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AbstractBradykinin is a potent vasoactive nonapeptide. It elicits a rise in cytosolic Ca2+ (Ca2+)(i) in endothelial cells, resulting in Call-dependent synthesis and release of endothelial vasoclilators. In the present study, we investigated the mechanism of bradykinin-induced Call influx in primary cultured rat aortic endothelial cells and in a mouse heart microvessel endothelial cell line (H5V). Bradykinin-induced Call influx was resolved into capacitative Call entry (CCE) and non-CCE. The non-CCE component was inhibited by a 132 receptor antagonist (HOE140; 1 mu M) and a phospholipase C (PLC) inhibitor (U73122; 10 mu M). The action of bradykinin could be mimicked by 1-oleoyl-2-acetyl-glycerol, an analogue of diacylglycerol (DAG), and by RHC80267, a DAG-lipase inhibitor. Immunoblots showed that TRPC6 was one of the main TRPC channels expressed in endothelial cells. Transfection of H5V cells with two siRNA constructs against TRPC6 both markedly reduced the TRPC6 protein level and, at the same time, decreased the percentage of cells displaying bradykinin-induced non-CCE. siRNA transfection also reduced the magnitude of non-CCE among the cells responding to bradykinin. Taken together, our data suggest that bradykinin-induced non-CCE is mediated via the B2-PLC pathway, and that DAG may be involved in this process. Further, TRPC6 is one of the important channels participating in bradykinin-induced non-CCE in endothelial cells. Copyright (c) 2006 S. Karger AG, Basel.
All Author(s) ListLeung PC, Cheng KT, Liu CL, Cheung WT, Kwan HY, Lau KL, Huang Y, Yao XQ
Journal nameJournal of Vascular Research
Volume Number43
Issue Number4
Pages367 - 376
LanguagesEnglish-United Kingdom
Keywordsbradykinin; diacylglycerol; non-capacitative Ca2+ entry; phospholipase C; TRPC6
Web of Science Subject CategoriesCardiovascular System & Cardiology; Peripheral Vascular Disease; PERIPHERAL VASCULAR DISEASE; Physiology; PHYSIOLOGY

Last updated on 2020-24-09 at 01:42