[PAR (protease-activated receptor) as a novel target for development of gastric mucosal cytoprotective drugs].
Protease-activated receptor-2 (PAR-2), a G protein-coupled seven trans-membrane domain receptor, is distributed throughout the gastrointestinal tract, modulating various functions. In gastric mucosa, PAR-2 present in sensory neurons, upon activation, triggers mucus secretion by stimulating release of CGRP and tachykinins, resulting mucosal cytoprotection. PAR-2 activation also suppresses acid secretion and increase mucosal blood flow, contributing to the protective mechanisms. In contrast, PAR-2 is also present in chief cells, facilitating pepsinogen secretion. PAR-2 would thus appear to be primarily protective in gastric mucosa, but may also have an aggressive property in certain conditions. Finally, functions of PARs other than PAR-2 in gastric mucosa are also discussed.
Kawabata
Atsufumi
A
Department of Pathophysiology & Therapeutics, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan.
Kuroda
Ryotaro
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015195:Drug Design; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism; D005765:Gastrointestinal Agents; D006801:Humans; D020116:Pepsinogen A / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology; D015320:Tachykinins / Q000378:metabolism
D005765:Gastrointestinal Agents; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D015320:Tachykinins; D020116:Pepsinogen A; D015740:Calcitonin Gene-Related Peptide