title: Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats.
abstract: Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle. The PAR-2-activating peptide SLIGRL-NH(2), but not the inactive control peptide, when administered i.v., strongly suppressed gastric acid secretion in response to carbachol, pentagastrin or 2-deoxy-D-glucose in the rats with a pylorus ligation. The PAR-2-mediated suppression of acid secretion was resistant to cyclooxygenase inhibition or ablation of sensory neurons by capsaicin. Our results provide novel evidence that in addition to stimulating neurally mediated mucus secretion, activation of PAR-2 suppresses gastric acid secretion independently of prostanoid production or sensory neurons. These dual actions of PAR-2 would result in gastric mucosal cytoprotection.
authors.affiliation: Research and Development Center, Fuso Pharmaceutical Industries Ltd., 536-8523, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kawai
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nishimura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Araki
authors.forename: Bahjat
authors.initials: B
authors.lastname: Al-Ani
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Kuroda
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D003864:Depression, Chemical; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009842:Oligopeptides; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide