Chemerin-induced arterial contraction is G i- and calcium-dependent

Vascul Pharmacol. 2017 Jan;88:30-41. doi: 10.1016/j.vph.2016.11.009. Epub 2016 Nov 24.

Abstract

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.

Keywords: Chemerin; Signaling; Smooth muscle.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism*
  • Calcium / metabolism*
  • Calcium Channels, L-Type / metabolism
  • Chemokines / administration & dosage
  • Chemokines / metabolism*
  • Dose-Response Relationship, Drug
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Hypertension / physiopathology
  • Intercellular Signaling Peptides and Proteins / administration & dosage
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • rho-Associated Kinases / metabolism

Substances

  • Calcium Channels, L-Type
  • Chemokines
  • Intercellular Signaling Peptides and Proteins
  • Rarres2 protein, rat
  • rho-Associated Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Calcium