Effects of cholecystokinin on gastric injury and gastric mucosal blood flow.

Cholecystokinin (CCK) is a vasodilator and prevents gastric injury from ethanol. Its effects against other irritants are unknown. This study was conducted to (1) assess whether CCK or oleate, a CCK secretagogue, could prevent gastric injury from other damaging agents and (2) examine the role of blood flow in CCK-induced gastroprotection. Conscious rats were pretreated for 10 minutes with intravenous saline solution or CCK (5 nmol/kg) or were given 1 ml of orogastric water or oleate (100 mmol/L) 30 minutes before a 1 ml orogastric bolus of acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), 0.75N hydrochloric acid, or 0.2N sodium hydroxide. Rats were killed 5 minutes after receiving an irritant and the total area (mm2) of macroscopic injury was quantified. The duration of CCK-induced gastroprotection against acidified ethanol was examined at 5, 10, 30, and 60 minutes after its administration. Other rats had gastric mucosal blood flow determined (fluorescent microspheres) at identical time points. CCK and oleate decreased gastric injury from all three luminal irritants. CCK-induced gastroprotection was present for 30 minutes but only enhanced gastric mucosal blood flow at 5 and 10 minutes. These data suggest that endogenous CCK may play a role in gastric mucosal defense and that blood flow alone does not fully explain CCK gastroprotection.