title: Chemerin-induced arterial contraction is Gi- and calcium-dependent.
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 S157isoform) caused a concentration-dependent contraction of isolated aorta (EC50100nM) and elicited a concentration-dependent intracellular calcium response (EC5010nM). Pertussis toxin (Giinhibitor), 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 Giproteins 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.
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States. Electronic address: ferlandd@msu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ferland
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Darios
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Neubig
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Benita
authors.initials: B
authors.lastname: Sjögren
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Truong
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Rosa
authors.initials: R
authors.lastname: Torres
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Dexheimer
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Thompson
authors.affiliation: Department of Pharmacology and Toxicology, 1355 Bogue Street Rm B445, Michigan State University, East Lansing, MI 48824-1317, United States.
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D018925:Chemokines / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C560738:Rarres2 protein, rat; D054460:rho-Associated Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium
keywords: Chemerin; Signaling; Smooth muscle