CHOLECYSTOKININ-INDUCED PROTECTION AGAINST GASTRIC INJURY IS INDEPENDENT OF ENDOGENOUS SOMATOSTATIN

Cholecystokinin (CCK) prevents macroscopic injury to the stomach from luminal irritants by an unknown mechanism. The present study was under taken in conscious rats to ascertain what role gastric mucosal blood f low, sensory neurons, and endogenous somatostatin play in CCK-induced gastric protection. Subcutaneous administration of CCK (10-100 mu g/kg ) significantly reduced macroscopic injury to the acid-secreting porti on of the stomach caused by 1 ml of orally administered acidified etha nol (150 mM HCl, 50% ethanol) and augmented gastric mucosal blood flow (fluorescent microspheres) in a dose-dependent fashion. However, alth ough the protective response to CCK (100 mu g/kg) was still present at 2 h, the blood flow response had returned to baseline by 45 min. Abla tion of capsaicin-sensitive afferent neurons with capsaicin (125 mg/kg sc) did not negate CCK-induced protection. Pretreatment with exogenou s somatostatin (1 pmol-1 nmol/kg sc) failed to prevent the damaging ef fects of acidified ethanol to gastric mucosa. Immunoneutralization of endogenous somatostatin with somatostatin monoclonal antibody (2 mg ip ) did not reverse the protective actions of CCK. Thus the data suggest that although CCK may prepare the gastric mucosa to withstand a damag ing insult by augmenting gastric mucosal blood flow its protective mec hanism is independent of intact sensory neurons and endogenous somatos tatin.