Chemerin-induced arterial contraction is Gi- and calcium-dependent.

Vascular pharmacology (2016-11-29)
David J Ferland, Emma S Darios, Richard R Neubig, Benita Sjögren, Nguyen Truong, Rosa Torres, Thomas S Dexheimer, Janice M Thompson, Stephanie W Watts
摘要

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 100nM) and elicited a concentration-dependent intracellular calcium response (EC50 10nM). 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.

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Sigma-Aldrich
人血管紧张素 II, ≥93% (HPLC), powder
Sigma-Aldrich
单克隆抗-肌动蛋白,α-平滑肌-FITC 小鼠抗, clone 1A4, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
百日咳毒素 来源于百日咳杆菌, lyophilized powder
Sigma-Aldrich
白蛋白 来源于鸡蛋白, lyophilized powder, ≥90% (agarose gel electrophoresis)
Sigma-Aldrich
Anti-phospho-Erk1/2 (Thr202/Tyr204, Thr185/Tyr187)Antibody, recombinant clone AW39R, rabbit monoclonal, clone AW39R, Upstate®, from rabbit
Sigma-Aldrich
Anti-α-Actin Mouse mAb (1A4), liquid, clone 1A4, Calbiochem®
Sigma-Aldrich
Chemerin human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC)