Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa: immunolocalization and facilitation of pepsin/pepsinogen secretion
作者:Naoyuki Kawao、Yuriko Sakaguchi、Ai Tagome、Ryotaro Kuroda、Shozo Nishida、Kiyohiro Irimajiri、Hiroyuki Nishikawa、Kenzo Kawai、Morley D Hollenberg、Atsufumi Kawabata
DOI:10.1038/sj.bjp.0704562
日期:2002.3
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.
PAR‐2‐like immunoreactivity was abundant in the deep regions of gastric mucosa, especially in chief cells.
The PAR‐2 agonist SLIGRL‐NH2, but not the control peptide LSIGRL‐NH2, administered i.v. repeatedly at 0.3 – 1 μmol kg−1, four times in total, significantly facilitated gastric pepsin secretion, although a single dose produced no significant effect.
The PAR‐2‐mediated gastric pepsin secretion was resistant to omeprazole, NG‐nitro‐L‐arginine methyl ester (L‐NAME) or atropine, and also to ablation of sensory neurons by capsaicin.
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.
British Journal of Pharmacology (2002) 135, 1292–1296; doi:10.1038/sj.bjp.0704562
蛋白酶激活受体-2 (PAR-2) 的激动剂会引发神经介导的粘液分泌,同时伴随胃黏膜的细胞保护作用。本研究对大鼠胃黏膜中的 PAR-2 进行免疫定位,并探讨 PAR-2 是否能调节大鼠的胃蛋白酶/胃蛋白酶原分泌。PAR-2 类似免疫反应的活性在胃黏膜的深层区域丰富存在,尤其是在主细胞中。PARG2激动剂SLIGRL-NH2,而不是对照肽LSIGRL-NH2,以0.3 - 1 μmol kg−1的剂量通过静脉给药,总共四次,显著促进了胃蛋白酶的分泌,尽管单次给药没有产生显著效果。PARG2介导的胃蛋白酶分泌对奥美拉唑、NG-硝基-L-精氨酸甲酯 (L-NAME) 或阿托品具有耐药性,并且对抗辣椒素引起的传入神经元的消除具有耐药性。因此,我们的研究为 PAR-2 定位于黏膜主细胞并促进大鼠胃蛋白酶分泌提供了新的证据,这很可能是通过直接机制实现的。英国药理学杂志 (2002) 135, 1292–1296;doi:10.1038/sj.bjp.0704562