The role of prostaglandin D2 in the genesis of indomethacin-induced gastric lesions in rats.
Four kinds of prostaglandins (PGs), 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2, in rat gastric mucosa were decreased at 1 or 6 h after oral administration of indomethacin (2 or 12 mg/kg). With 2 mg/kg of indomethacin, the PG levels had slightly recovered 6 h later. Gastric lesions were observed 6 h after administration of indomethacin (12 mg/kg), but not with 2 mg/kg. Omeprazole (20 mg/kg, i.p.) prevented ulcer formation caused by indomethacin, without improvement of the reduced gastric mucosal PG levels. PGD2 (0.5 mg/kg, p.o.) reduced indomethacin-induced gastric lesions and considerable amounts of PGD2 existed in the gastric mucosa. We conclude that H+ is a determining factor in the genesis of indomethacin-induced gastric lesions and persistent decreases in tissue PG levels also participate in ulcer formation.
Goto
H
H
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Nakazawa
S
S
Segawa
K
K
Tsukamoto
Y
Y
Hase
S
S
Arisawa
T
T
Osada
T
T
Kawabe
Y
Y
Kuroiwa
M
M
Tsuchida
T
T
D000818:Animals; D001696:Biomechanical Phenomena; D005753:Gastric Mucosa / Q000378:metabolism; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced
D011453:Prostaglandins; D009853:Omeprazole; D015230:Prostaglandin D2; D007213:Indomethacin