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 were investigated in the rat and correlated with the cytoprotective action of this agent. Oral administration of capsaicin induced a concentration-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 protection was significantly attenuated by chemical deafferentation or pretreatment with indomethacin (5 mg kg-1, s.c.). Capsaicin, given intragastrically or applied topically to the mucosa, produced significant changes in various gastric functions at different dose levels; inhibition 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 cytoprotection, were significantly mitigated by either chemical deafferentation or indomethacin pretreatment, yet their dose-response relationships showed that the effective dose range for cytoprotection was close to that for motility inhibition but much higher than that for the mucosal blood flow response. These data suggest that the cytoprotective action of capsaicin may be functionally associated with gastric motility inhibition rather than increase of mucosal blood flow.