Oral but not parenteral aspirin upregulates COX-2 expression in rat stomachs. a relationship between COX-2 expression and PG deficiency.
OBJECTIVE
We compared the ulcerogenic effects of aspirin (ASA) and indomethacin in the rat gastric mucosa depending on the route of administration, together with the expression of COX-2.


METHODS
Animals fasted for 18 h were given ASA or indomethacin, either p.o. or s.c., and the stomach was examined 4 h later.


RESULTS
Indomethacin decreased mucosal PGE(2 )level, increased gastric motility, and caused gastric lesions with the up-regulation of COX-2 expression, irrespective of the route of administration. ASA induced both damage and COX-2 expression in the stomach when given p.o. but not s.c., despite decreasing the PGE(2) level similarly via either route of administration. Gastric motility was temporarily increased and gastric potential difference (PD) was markedly decreased by ASA given p.o. PGE(2) and atropine, although preventing ASA-induced gastric lesions as well as hypermotility, affected neither the COX-2 expression nor PD reduction induced by p.o. ASA. By contrast, the COX-2 expression induced by indomethacin was prevented by both PGE(2) and atropine.


CONCLUSIONS
ASA given p.o. caused damage in the stomach, together with the up-regulation of COX-2 expression, and this expression may be due to the topical irritative action, rather than being a result of PG deficiency. The expression of COX-2 after indomethacin is associated with gastric hypermotility due to PG deficiency.
Mashita
Yuji
Y
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.
Taniguchi
Masaki
M
Yokota
Aya
A
Tanaka
Akiko
A
Takeuchi
Koji
K
D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D015870:Gene Expression; D007213:Indomethacin / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D011458:Prostaglandins E; D051546:Cyclooxygenase 2; D001241:Aspirin; D007213:Indomethacin