Abstracts
1997 Digestive Disease Week

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

JM Cross, L Chang, DW Mercer. Department of Surgery, University of Texas Houston Medical School, Houston, TX.

CCK is a vasodilator and prevents gastric injury from ethanol, but not aspirin. The protective actions of this peptide against other irritants are unknown. This study was conducted to (1) characterize the time course of CCK induced hyperemia and gastroprotection, (2) assess whether this peptide prevents gastric injury from other damaging agents, and (3) determine whether oleate, a CCK secretagogue, has gastroprotective actions. Conscious adult rats were given intravenously either saline or CCK (5 nmol/kg) 10, 30, or 60 minutes before a 1 ml orogastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Rats were sacrificed 5 min after receiving the irritant and the total area (mm²) of macroscopic injury quantified. Additional rats had GMBF determined (fluorescent microspheres) at similar timepoints. In other experiments, CCK or saline was given 10 min before 1 ml of orogastric 0.75N HCl or 0.2N NaOH and macroscopic damage assessed 5 min after administration of these irritants. Lastly, 1 ml of orogastric saline or oleate (100 mM) was given 30 min before induction of gastric injury with acidified ethanol and gastric injury determined. Data are reported as mean ± SEM (N >= 4/group; ANOVA). These studies demonstrated that CCK significantly (p < 0.001) decreased gastric injury from acidified ethanol at 10 min (6 ± 3 mm^{2}) and 30 min (35 ± 8 mm²), but not at 60 min (125 ± 12 mm²) when compared to saline pretreated rats (136 ± 16 mm²). CCK also prevented the damaging effects of concentrated acid (9 ± 5 vs 175 ± 15 mm^{2}; p < 0.001) and base (12 ± 6 vs 153 ± 16 mm²; p < 0.001). Oleate likewise resulted in gastroprotection from acidified ethanol when compared to controls (40 ± 9 vs 120 ± 8 mm²; p < 0.001). In the absence of an irritant, CCK significantly (p < 0.05) increased GMBF at 10 min, but not at 30 or 60 min (396 ± 45 vs 116 ± 15 vs 115 ± 19 ml/min/100g tissue) when compared to controls (112 ± 8 ml/min/100g tissue). GMBF in rats pretreated for 10 min with CCK followed by exposure of the stomach to acidified ethanol for 5 min did not differ from saline pretreated controls given this irritant (186 ± 29 vs 163 ± 21 ml/min/100g tissue; p = NS). These data suggest that endogenous CCK may play a role in gastric mucosal defense and CCK-induced protection may involve factors in addition to hyperemia, since GMBF is at baseline 30 min after its administration, a timepoint when gastroprotection is still present.