GASTROPROTECTIVE ACTIONS OF BOMBESIN, L-DOPA, AND MILD IRRITANTS - ROLES OF PROSTAGLANDINS AND SENSORY NEURONS

Background. Bombesin and dopamine prevent gastric injury by an unknown mechanism. Sensory neurons and endogenous prostaglandins play an impo rtant rob in gastric mucosal defense. This study was designed to asses s the rot of these two local defense mechanisms in bombesin and dopami ne-induced gastroprotection, as well as mild irritant-induced adaptive cytoprotection. Methods. Conscious, fasted rats were given either cap saicin (125 mg/kg subcutaneously) to ablate sensory neurons or indomet hacin (5 mg/kg intraperitoneally) to inhibit prostaglandin synthesis, 2 weeks and 30 minutes, respectively, before administration of bombesi n (100 mu g/kg subcutaneously), the dopamine precursor L-DOPA (25 mg/k g intraperitoneally), or the mild irritant 25 % ethanol (1 mL orogastr ic). A 1-mL orogastric bolus of acidified ethanol (150 mmol/L HCl/50 % ethanol) was given 30 minutes after pretreatment with these peptides and 15 minutes after administration of the mild irritant. Rats were ki lled 5 minutes later and the total area of macroscopic gastric injury quantified. Results. Ablation of sensory neurons with capsaicin negate d the protective actions of bombesin but failed to reverse gastroprote ction by L-DOPA or 25 % ethanol. Cyclooxygenase inhibition with indome thacin partially reversed bombesin and mild irritant-induced gastropro tection but did not diminish the protective actions of L-DOPA. Conclus ions. Bombesin requires intact sensory neurons to exert protective act ions through a mechanism mediated, at least in part, by endogenous pro staglandins. Adaptive cytoprotection by the mild irritant 25 % ethanol requires the presence of endogenous prostaglandins but not sensory ne urons. L-DOPA-induced gastroprotection is independent of both local de fense mechanisms.