Cyclooxygenase inhibition attenuates cholecystokinin-induced gastroprotection.
Cholecystokinin prevents gastric injury by an unknown mechanism. This study was conducted in conscious, fasted female rats in order to assess the role of endogenous prostaglandins as a potential protective mechanism for cholecystokinin-induced gastroprotection. Intravenous administration of cholecystokinin (0.05-5 nmol/kg) dose-dependently reduced macroscopic injury to the glandular portion of the stomach caused by 1 ml of orally administered acidified ethanol (150 mM hydrochloric acid-50% ethanol), an effect corroborated by histologic analysis. In time course studies, this protective action occurred as early as 10 min following cholecystokinin injection (5 nmol/kg intravenously), but was absent at 1 hr. Cyclooxygenase inhibition with either indomethacin (5 mg/kg intraperitoneally) or aspirin (100 mg/kg intraperitoneally) resulted in a partial reversal in cholecystokinin-induced gastroprotection, effects that were similar in magnitude. However, while indomethacin reduced gastric mucosal prostaglandin synthesis (enzyme-linked immunoassay) by 60%, aspirin almost totally abolished prostaglandin synthesis (95% reduction). Cholecystokinin (5 nmol/kg intravenously) did not significantly enhance gastric mucosal prostaglandin synthesis in the absence of cyclooxygenase inhibition. These data indicate that cholecystokinin requires the presence of endogenous prostaglandins in order to fully exert its gastroprotective actions. However, release of endogenous prostaglandins does not entirely explain the protective response, and additional factors likely participate in this action.
Mercer
D W
DW
Department of Surgery, The University of Texas-Houston Medical School, 77030, USA.
Smith
G S
GS
Miller
T A
TA
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology* / Q000502:physiology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D005765:Gastrointestinal Agents; D011453:Prostaglandins; D000431:Ethanol; D012844:Sincalide; D001241:Aspirin; D007213:Indomethacin