Investigating a Novel Receptor that Mediates Vasoconstriction in Mouse Femoral Arteries

Joselia Carlos, The University of Western Ontario

Abstract

The synthetic peptide trans-cinnamoyl-leucine-isoleucine-glycine-arginine-leucine-ornithine-amide (tcLIGRLO) causes smooth muscle contraction in mouse femoral arteries. The identity of the receptor that mediates this response is undetermined. We hypothesize that the novel mechanism for tcLIGRLO-induced contractions involves a G-protein coupled receptor (GPCR) and a G_q-Ca²⁺ signalling pathway. Chapter 2 describes experiments using femoral arteries isolated from male and female systemic protease-activated receptor 2 (PAR2KO) mice (n=31; 21 – 39 weeks of age) using tcLIGRLO and the G_q-inhibitor, YM-254890 (YM). Contractions produced by tcLIGRLO did not differ by sex but decreased as age increased. YM inhibited tcLIGRLO-induced contractions. Chapter 3 describes preliminary work to identify a human GPCR for tcLIGRLO, other than PAR2, using the TANGO assay to screen four candidates. We identified a potential human GPCR target that warrants additional study. In conclusion, tcLIGRLO activates a novel mechanism involving a G_q-coupled receptor. This novel mechanism may have potential significance in vascular biology.