Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats.
Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO3- secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO3- secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE2 (10 micrograms/kg), which reduced acid secretion and motility and increased gastric HCO3- secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE2), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin.
Ueki
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takeuchi
K
K
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000627:therapeutic use; D001639:Bicarbonates / Q000378:metabolism; D002927:Cimetidine / Q000008:administration & dosage / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D007279:Injections, Subcutaneous; D008297:Male; D010528:Peristalsis / Q000187:drug effects; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000503:physiopathology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology* / Q000517:prevention & control
D001639:Bicarbonates; D001285:Atropine; D002927:Cimetidine; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin