Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa: immunolocalization and facilitation of pepsin/pepsinogen secretion.
1. Agonists of protease-activated receptor-2 (PAR-2) trigger neurally mediated mucus secretion accompanied by mucosal cytoprotection in the stomach. The present study immunolocalized PAR-2 in the rat gastric mucosa and examined if PAR-2 could modulate pepsin/pepsinogen secretion in rats. 2. PAR-2-like immunoreactivity was abundant in the deep regions of gastric mucosa, especially in chief cells. 3. The PAR-2 agonist SLIGRL-NH(2), but not the control peptide LSIGRL-NH(2), administered i.v. repeatedly at 0.3 - 1 micromol kg(-1), four times in total, significantly facilitated gastric pepsin secretion, although a single dose produced no significant effect. 4. The PAR-2-mediated gastric pepsin secretion was resistant to omeprazole, N(G)-nitro-L-arginine methyl ester (L-NAME) or atropine, and also to ablation of sensory neurons by capsaicin. 5. Our study thus provides novel evidence that PAR-2 is localized in mucosal chief cells and facilitates gastric pepsin secretion in the rats, most probably by a direct mechanism.
Kawao
Naoyuki
N
School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
Sakaguchi
Yuriko
Y
Tagome
Ai
A
Kuroda
Ryotaro
R
Nishida
Shozo
S
Irimajiri
Kiyohiro
K
Nishikawa
Hiroyuki
H
Kawai
Kenzo
K
Hollenberg
Morley D
MD
Kawabata
Atsufumi
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism*; D020116:Pepsinogen A / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000502:physiology
D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D001285:Atropine; D020116:Pepsinogen A; D010434:Pepsin A; D009853:Omeprazole; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester