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TRPV 4 activates cytosolic phospholipase A 2 via Ca 2+ ‐dependent PKC / ERK 1/2 signalling in controlling hypertensive contraction
Author(s) -
Li Hongjuan,
Kan Hao,
He Chao,
Zhang Xiaodong,
Yang Zhenyu,
Jin Jian,
Zhang Peng,
Ma Xin
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12959
Subject(s) - trpv , protein kinase c , mapk/erk pathway , chemistry , contraction (grammar) , phospholipase a2 , endocrinology , phospholipase c , rho associated protein kinase , medicine , kinase , pharmacology , transient receptor potential channel , biochemistry , signal transduction , receptor , enzyme , trpv1
Summary Activation of TRPV 4 (transient receptor potential vanilloid 4) has been reported to result in endothelium‐dependent contraction in the aortae of hypertensive mice. This contraction involved increased cPLA 2 (cytosolic phospholipase A 2 ) activity. The mechanism by which TRPV 4 regulates cPLA 2 activity to induce contraction in hypertension, however, is unknown. Through measurements of arterial tension and protein level, we showed that high‐salt diet induced hypertension increases activity of PKC (protein kinase C) and ERK 1/2 (extracellular signal‐regulated kinase 1/2). GSK 1016790A, a TRPV 4 agonist and AC h (acetylcholine) induced contractions were suppressed by Go6983, a PKC inhibitor and PD 98059, an ERK 1/2 inhibitor. TRPV 4 activation increased activity of PKC and ERK 1/2 in endothelial cells from hypertensive mice and this response was suppressed by HC 067047, a TRPV 4 inhibitor and BAPTA / AM , a Ca 2+ chelator. PLA 2 assay and western blotting showed that blocking of PKC or ERK 1/2 inhibited TRPV 4 or AC h‐induced cPLA 2 activity. Enzyme immunoassay showed that GSK 1016790A or AC h triggered the release of PGF 2α (prostaglandin F 2α ) was reduced by inhibition of PKC or ERK 1/2. These data further suggest Ca 2+ / PKC / ERK 1/2 axis as a novel mechanism for TRPV 4 in the activation of cPLA 2 in hypertension.