Chemerin-induced arterial contraction is G_i- and calcium-dependent

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• 作者：David J. Ferland ; ^{ferlandd@msu.edu} ; Emma S. Darios ; Richard R. Neubig ; Benita Sjö ; gren ; Nguyen Truong ; Rosa Torres ; Thomas S. Dexheimer ; Janice M. Thompson ; Stephanie W. Watts
• 关键词：Akt ; protein kinase B ; ANG II ; angiotensin II ; CaM ; calmodulin ; CCRL2 ; chemokine (CC motif) receptor-like 2 ; CMKLR1 ; chemokine-like receptor 1 ; Erk MAPK ; extracellular signal-regulated kinase mitogen activated protein kinase ; GAP ; GTPase activating protein ; GEF ; guanine nucleotide exchange factor ; GPR1 ; G protein-coupled receptor 1 ; MLC ; myosin light-chain ; MLCK ; myosin light-chain kinase ; MLCP ; myosin light-chain phosphatase ; PD098059 ; 2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one ; PE ; phenyleph
• 刊名：Vascular Pharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：88
• 期：Complete
• 页码：30-41
• 全文大小：1792 K
• 卷排序：88

文摘

Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinetics of rat aortic smooth muscle cells to assess the possible signaling pathway. Chemerin-9 (nonapeptide of the chemerin S157 isoform) caused a concentration-dependent contraction of isolated aorta (EC50 100 nM) and elicited a concentration-dependent intracellular calcium response (EC50 10 nM). Pertussis toxin (Gi inhibitor), verapamil (L-type Ca2 + channel inhibitor), PP1 (Src inhibitor), and Y27632 (Rho kinase inhibitor) reduced both calcium influx and isometric contraction to chemerin-9 but PD098059 (Erk MAPK inhibitor) and U73122 (PLC inhibitor) had little to no effect on either measure of chemerin signaling. Although our primary aim was to examine chemerin signaling, we also highlight differences in the mechanisms of chemerin-9 and recombinant chemerin S157. These data support a chemerin-induced contractile mechanism in vascular smooth muscle that functions through Gi proteins to activate L-type Ca2 + channels, Src, and Rho kinase. There is mounting evidence linking chemerin to hypertension and this mechanism brings us closer to targeting chemerin as a form of therapy.