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.
Tramontana
M
M
Institute of Internal Medicine IV, School of Medicine, University of Florence, Italy.
Del Bianco
E
E
Cecconi
R
R
Maggi
C A
CA
Geppetti
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D012430:Ruthenium Red; D013779:Tetrodotoxin; D014701:Veratridine; D009543:Nifedipine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin