Endothelial cell transient receptor potential channel C5 (TRPC5) is essential for endothelium-dependent contraction in mouse carotid arteries
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AbstractAugmented endothelium-dependent contractions (EDC) contributes to endothelial dysfunction and vascular disease progression. An early signal in EDC is cytosolic [Ca2+](i) rise in endothelial cells, which stimulates the production of contractile prostanoids, leading to vascular contraction. In this study, the molecular identity of Ca2+-permeable channels in endothelial cells and its function were investigated. Vascular tension was measured by wire myograph. EDCs were elicited by acetylcholine (ACH) in the presence of N-G-nitro-t-arginine methyl ester (L-NAME). [Ca2+]; was measured using a Ca2+-sensitive fluorescence dye. Enzyme Immunoassay (EIA) was used for prostaglandin measurement. Immunohistochemical staining found the expression of transient receptor potential channel C5 (TRPC5) in endothelial and smooth muscle cells of mouse carotid arteries. ACH-induced EDC in male mouse carotid arteries was found to be substantially reduced in TRPC5 knockout (KO) mice than in wild type (WT) mice. TRPC5 inhibitors clemizole and ML204 also reduced the EDC. Furthermore, ACH-induced Ca2+ entry in endothelial cells was lower in TRPC5 KO mice than in WT mice. Moreover, the EDC was abolished by a cyclooxygenase-2 (COX-2) inhibitor NS-398, but not affected by a COX-1 inhibitor valeryl salicylate (VAS). Enzyme immunoassay results showed that TRPC5 stimulated the COX-2-linked production of prostaglandin F-2 alpha (PGF(2 alpha),), prostaglandin E-2 (PGE(2)), and prostaglandin D-2 (PGD(2)). Exogeneous PGF(2 alpha), PGE(2), and PGD(2) could induce contractions in carotid arteries. Our present study demonstrated that TRPC5 in endothelial cells contributes to EDC by stimulating the production of COX-2-linked prostanoids. The finding extends our knowledge about EDC.
All Author(s) ListCai LIANG, Yunting ZHANG, Duan ZHUO, Chun-Yin LO, Libo YU, Chi-Wai LAU, Yiu-Wa KWAN, Gary TSE, Yu HUANG, Xiaoqiang YAO
Journal nameBiochemical Pharmacology
Detailed descriptionLast and Corresponding author: YAO Xiaoqiang
Volume Number159
Pages11 - 24
LanguagesEnglish-United Kingdom
KeywordsTRPC5, Endothelial cells, EDC, COX-2, EDCF, Prostanoid
Web of Science Subject CategoriesPharmacology & Pharmacy;Pharmacology & Pharmacy

Last updated on 2020-24-10 at 03:49