ChemR23 Receptor signals through pro‐contractile signaling pathways

Abstract

(Pro)Chemerin is a peptide secreted from fat and the liver. Chemerin activates ChemR23 to elicit arterial contraction when endothelium is dysfunctional. The signaling of ChemR23 receptor in smooth muscle is unknown. Therefore, we tested the hypothesis that the ChemR23 receptor signals through pro‐contractile pathways using the thoracic aorta of the female rat. Immunohistochemistry supported the presence of ChemR23 receptor in aortic media. Aortic rings lacking endothelium were mounted in tissue baths for measurement of isometric contraction and cumulative responses to Chemerin‐9, an agonist of ChemR23, developed. Tissues were incubated with a signaling inhibitor or vehicle for one hour. Nifedipine reduced the maximum contraction to chemerin‐9 [Veh = 47% ± 12% maximum phenylephrine contraction vs Nif (1 uM) =5% ± 0.7%], as did the Rho Kinase inhibitor Y27632 [Veh = 32% ± 16%, Y27632 (10 uM) =0.8% ± .3%], protein kinase C inhibitor Chelerythrine [Veh = 57%± 12%, Chel (10 uM) =0.1% ± 2%] and p38 MAPK inhibitor SB203580 [Veh= 56% ± 12%, SB203580 (10 uM) =19% ± 5%]. The phosphoinoside‐3 kinase inhibitor LY294002 also reduced contraction [Veh = 57± 16%, LY294002 (10 uM) =26% ± 8]. By contrast, Erk MAPK inhibitor PD09859 did not reduce chemerin‐9 induced contraction. These findings suggest the ChemR23 receptor signals through pro‐contractile signaling pathways. Supported by REPID.