Reduced adaptive cytoprotection by hyperosmotic saline in IP knockout mice

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.69-69
• Main Authors: Boku, Katsuharu, Saeki, Takeo, Ohno, Takashi, Kamata, Kazuhisa, Saigenji, Katsunori, Hayashi, Izumi, Katori, Makoto, Murata, Takahiko, Narumiya, Shuh, Majima, Masataka
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)47742-1

Intragastric administration of 1M NaCl (Na) increased prostaglandins (PGs). Fifty% ethanol (EtOH) after Na released CGRP, and inhibited EtOH-induced gastric mucosal injury. We tested whether or not PGI_2 generated by Na has a role in prevention of mucosal injury through the release of CGRP using IP receptor knockout mice. Stomach of C57/BL6 mice was doubly cannulated, and was perfused with physiological saline, Na or EtOH. In some animals, CGRP8-37 or indomethacin was injected before 1M NaCl perfusion. Result： 1) Wild type mice： EtOH; The injured area was 19.8%. Na → EtOH; The injured area was reduced to 12.2%. Pretreatment with CGRP8-37 restored the injured area (19.0%). Pretreatment with IDM restored the injured area (21.1%). 2) IP knockout mice： EtOH; The injured area was 20.3%. Na → EtOH; The injured area was not reduced (18.8%). Conclusions： The present results suggested that the endogenous PGI_2 generated by Na may prevent EtOH-induced mucosal injury through the enhancement of CGRP release.