RT Journal Article
SR Electronic
T1 Cyclooxygenase Isozymes Involved in Adaptive Functional Responses in Rat Stomach after Barrier Disruption
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 713
OP 719
DO 10.1124/jpet.103.054973
VO 307
IS 2
A1 Masanori Takeeda
A1 Masanori Yamato
A1 Shinichi Kato
A1 Koji Takeuchi
YR 2003
UL http://jpet.aspetjournals.org/content/307/2/713.abstract
AB We investigated the preferential role of cyclooxygenase (COX) isozymes in various functional changes of the rat stomach after exposure to taurocholate (TC) as a mild irritant. Under urethane anesthesia, a rat stomach mounted in an ex vivo chamber was perfused with saline or acid (50 mM HCl), and transmucosal potential difference (PD), gastric mucosal blood flow (GMBF), and acid secretion were measured before and after exposure of the stomach to 20 mM TC for 30 min. Indomethacin, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) (a selective COX-1 inhibitor), or rofecoxib (a selective COX-2 inhibitor) was given intraduodenally 30 min before the TC treatment. Mucosal application of TC caused a marked reduction in PD, followed by a decrease of acid secretion and an increase of GMBF. Previous administration of indomethacin did not affect the reduction in PD but significantly mitigated the two other responses induced by TC, resulting in a delay in the recovery in PD. These effects were mimicked by SC-560 but not rofecoxib, although neither of these drugs had any effect on the reduction in PD. Perfusion of TC-treated stomachs with 50 mM HCl caused only minimal damage, yet this treatment produced gross lesions in the presence of indomethacin or SC-560. Mucosal exposure to TC increased prostaglandin E2 production, but the response was inhibited by both indomethacin and SC-560 but not rofecoxib. These results suggested that COX-1 but not COX-2 is a key enzyme for regulating the functional alterations of the stomach and for maintaining the mucosal integrity after barrier disruption. The American Society for Pharmacology and Experimental Therapeutics