Veratridine evokes release of calcitonin gene-related peptide from capsaicin-sensitive nerves of rat urinary bladder.

The effect of superfusion with veratridine on the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was studied in slices of rat urinary bladder. Exposure to veratridine (1-200 microM) produced a concentration-related release of CGRP-LI. Veratridine (50 microM)-evoked CGRP-LI release was abolished in slices pre-exposed to capsaicin (10 microM for 40 min) or superfused in a Ca(2+)-free medium containing 1 mM EDTA. After exposure to veratridine (50 microM for 40 min), capsaicin (10 microM) was still able to release CGRP-LI. CGRP-LI release evoked by veratridine (50 microM) was inhibited by about 60% by tetrodotoxin (0.3 microM), attenuated (30%) by nifedipine (1 microM), and not affected by omega-conotoxin (0.1 microM). The capsaicin antagonist ruthenium red (10 microM) did not affect veratridine (50 microM)-evoked CGRP-LI release. The present results indicate that depolarization by veratridine induces CGRP-LI release from capsaicin-sensitive nerve fibres, an effect that is entirely dependent on extracellular Ca2+. The Ca2+ influx that promotes CGRP-LI release is mediated mostly by nifedipine-, omega-conotoxin- and ruthenium red-insensitive channels.