PROTECTIVE ACTION OF GASTRIN-17 AGAINST ALCOHOL-INDUCED GASTRIC INJURY IN THE RAT - ROLE IN MUCOSAL DEFENSE

Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant 25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the release of CCK as well as gastrin, which is structur ally similar to CCK. This study was undertaken in conscious rats to ex amine the gastroprotective actions of gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive cytoprotection with etha nol as the mild irritant. Intravenous (1-25 pmol/kg) administration of gastrin-17 dose dependently increased gastric mucosal blood flow (las er Doppler) and reduced gastric injury caused by 1 mi of orally admini stered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprote ction was achieved with the gastrin secretagogue 5% peptone (1 mi orog astrically). The gastroprotective capabilities of gastrin-17 were atte nuated by the type B CCK (gastrin) receptor antagonist L-365,260 (12.5 -25 mg/kg ip) and by capsaicin desensitization (125 mg/kg sc). CCK oct apeptide (5 nmol/kg iv)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg ip). Neither receptor antagoni st, alone or in combination, reversed the protective effects of the mi ld irritant 25% ethanol (1 mi orogastrically). Thus, whereas gastrin m ay play a role in gastric mucosal defense, neither CCK nor gastrin app ears to participate in the phenomenon of adaptive cytoprotection.