Physiological functions of protease-activated receptor-2

Abstract

Protease-activated receptors (PARs) are a family of G-protein-coupled-seven-trans-membrane-domain-receptors activated by specific proteases, consisting of four family members. PAR-2, a receptor activated by trypsin, tryptase or coagulation factors VIIa and Xa, is unevenly distributed throughout the mammalian body, modulating multiple physiological functions. In the gastrointestinal tract, PAR-2 is involved in gastric mucosal cytoprotection, smooth muscle motility modulation, salivary and pancreatic exocrine secretion, intestinal ionic transport, etc. In the circulatory system, endothelial PAR-2, upon activation, induces vascular relaxation by mechanisms dependent on nitric oxide or endothelium-derived hyperpolarizing factor (EDHF), resulting in hypotension in vivo. In the respiratory system, PAR-2 appears to play a dual role, being pro- and anti-inflammatory. In the nervous system, PAR-2 present in capsaicin-sensitive sensory neurons participates in processing of pain information. PAR-2 is thus involved in a variety of physiological and pathophysiological functions. PAR-2 is now considered one of the most important molecules as a target for drug development.