GASTRIC CYTOPROTECTION INDUCED BY CAPSAICIN IN THE RAT - RELATION TO MOTILITY, BLOOD-FLOW AND HCO3- SECRETION

The dose-response effects of capsaicin on various gastric functions we re investigated in the rat and correlated with the cytoprotective acti on of this agent. Oral administration of capsaicin induced a concentra tion-dependent reduction in the severity of gastric lesions induced by acidified ethanol (60% in 150 mM HCl, p.o.), and a significant effect was obtained at the concentration of 0.6 mg ml-1 or greater. This pro tection was significantly attenuated by chemical deafferentation or pr etreatment with indomethacin (5 mg kg-1, s.c.). Capsaicin, given intra gastrically or applied topically to the mucosa, produced significant c hanges in various gastric functions at different dose levels; inhibiti on of gastric motility (> 0.6 mg ml-1), increase of mucosal blood flow (> 0.03 mg ml-1) and stimulation of HCO3- secretion (> 0.3 mg ml-1), but did not affect acid secretion. These effects, similar to the cytop rotection, were significantly mitigated by either chemical deafferenta tion or indomethacin pretreatment, yet their dose-response relationshi ps showed that the effective dose range for cytoprotection was close t o that for motility inhibition but much higher than that for the mucos al blood flow response. These data suggest that the cytoprotective act ion of capsaicin may be functionally associated with gastric motility inhibition rather than increase of mucosal blood flow.