CALCITONIN-GENE-RELATED PEPTIDE PROTECTS CULTURED RAT GASTRIC-MUCOSALCELLS

Capsaicin exerts its gastroprotective effect by stimulating primary af ferent neurons, releasing calcitonin gene-related peptide (CGRP), whic h in turn increases gastric blood flow. In this work, the effects of c apsaicin, rat alpha-CGRP, and relative peptides hCGRP(8-37) and beta-h CGRP, and substance P on cultured gastric mucosal cells independent of neural and vascular mechanisms were studied, Damage was produced by i ndomethacin, ethanol or taurocholate (4,5-dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide and trypan blue exclusion tests were used to assess viability of the cultured cells, Capsaicin administration alon e did not injure gastric cells, However, capsaicin pretreatment potent iated the damaging effect of indomethacin and ethanol, In the sodium t aurocholate model, capsaicin slightly protected the cells against inju ry. alpha-rCGRP was protective against indomethacin, ethanol and tauro cholate in a dose-dependent manner, hCGRP(8-37) and beta-hCGRP both do se-dependently prevented injury caused by indomethacin at concentratio ns about eight times higher than that of alpha-rCGRP, but substance P was ineffective in the three different damage models, A combination of alpha-CGRP and hCG RP8-37 was also protective against indomethacin da mage to a similar extent as use of either agent alone, The defence mec hanism of capsaicin against gastric cell injury may in part be mediate d by a direct effect of CGRP on gastric mucosal cells, in addition to effects dependent on neural and vascular mechanisms, hCGRP(8-37) has n o antagonist effect against CGRP in this model, suggesting that CGRP r eceptors in this model may be different from those in other tissues. ( C) 1998 Lippincott-Raven Publishers.