Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones.
In the superfused isolated rat urinary bladder, capsaicin as well as electrical field stimulation evoked the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP, threshold 2 microM) reduced both, the capsaicin- and the electrical field stimulation-evoked release of CGRP-IR while a low concentration of Ruthenium Red (RR, 0.6 microM and 2 microM) selectively attenuated the capsaicin-evoked release of CGRP-IR but did not influence the effect of electrical field stimulation. 20 microM RR nearly abolished the capsaicin-evoked release, but also attenuated the effect of electrical field stimulation. In the isolated guinea-pig bronchus, electrical field stimulation and capsaicin induced non-cholinergic contractions which are known to be caused by tachykinin release from afferent nerve terminals. CCCP (0.6 microM) only reduced the response to field stimulation; a ten-fold higher concentration of CCCP attenuated field stimulation as well as capsaicin-induced contractions. This is in contrast to the reported selective inhibition of capsaicin-induced contractions by RR. The present data demonstrate that CCCP generally inhibits evoked neuropeptide release, regardless of the kind of stimulation used while low concentrations of RR preferentially inhibit capsaicin-evoked neuropeptide release.
Amann
R
R
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Maggi
C A
CA
Giuliani
S
S
Donnerer
J
J
Lembeck
F
F
D000818:Animals; D001980:Bronchi / Q000294:innervation / Q000378:metabolism / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000037:antagonists & inhibitors*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism
D009479:Neuropeptides; D009570:Nitriles; D012430:Ruthenium Red; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D012428:Ruthenium; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin