Calcitonin gene-related peptide protects cultured rat gastric mucosal cells

Capsaicin exerts its gastroprotective effect by stimulating primary afferent neurons, releasing calcitonin gene-related peptide (CGRP), which in turn increases gastric blood flow. In this work, the effects of capsaicin, rat alpha-CGRP, and relative peptides hCGRP(8-37) and beta-hCGRP, and substance P on cultured gastric mucosal cells independent of neural and vascular mechanisms were studied. Damage was produced by indomethacin, ethanol or taurocholate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue exclusion tests were used to assess viability of the cultured cells. Capsaicin administration alone did not injure gastric cells. However, capsaicin pretreatment potentiated the damaging effect of indomethacin and ethanol. In the sodium taurocholate model, capsaicin slightly protected the cells against injury. Alpha-rCGRP was protective against indomethacin, ethanol and taurocholate in a dose-dependent manner. hCGRP(8-37) and beta-hCGRP both dose-dependently prevented injury caused by indomethacin at concentrations 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 hCGRP(8-37) was also protective against indomethacin damage to a similar extent as use of either agent alone. The defence mechanism of capsaicin against gastric cell injury may in part be mediated by a direct effect of CGRP on gastric mucosal cells, in addition to effects dependent on neural and vascular mechanisms. hCGRP(8-37) has no antagonist effect against CGRP in this model, suggesting that CGRP receptors in this model may be different from those in other tissues.