title: Endothelium-dependent and -independent responses to protease-activated receptor-2 (PAR-2) activation in mouse isolated renal arteries.
abstract: Protease-activated receptors (PARs) are receptors which require proteolytic cleavage to be self-activated by newly exposed N-terminal 'tethered ligands', and hence serve as sensors for protelytic enzymes. While both the thrombin receptor (PAR-1) and PAR-2 (activated by tryptic enzymes) have been shown to mediate endothelium-dependent vasorelaxation, only PAR-1 has been shown to cause direct vascular smooth muscle contraction. In this study, we report that trypsin and the PAR-2 selective peptide ligand SLIGRL-NH2 not only caused endothelium-dependent relaxation of mouse renal arteries but also direct smooth muscle contraction if endothelial nitric oxide synthase was inhibited or if the endothelium was removed.
authors.affiliation: Department of Pharmacology, The University of Melbourne, Parkville, Australia.
authors.forename: J D
authors.initials: JD
authors.lastname: Moffatt
authors.forename: T M
authors.initials: TM
authors.lastname: Cocks
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects; D014357:Trypsin / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D019001:Nitric Oxide Synthase; D014357:Trypsin