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PMID: 10385248 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Respiratory action of capsaicin microinjected into the nucleus of the solitary tract: involvement of vanilloid and tachykinin receptors.

British journal of pharmacology ·Vol. 127 ·No. 2 ·1999-05-00 ·Pages 473-81

Mazzone SB, Geraghty DP

Abstract

1. The respiratory response to microinjection of capsaicin into the commissural nucleus of the solitary tract (cNTS) of urethane-anaesthetized rats was investigated in the absence and presence of the competitive vanilloid (capsaicin) antagonist, capsazepine, and selective tachykinin NK1, NK2 and NK3 antagonists (RP 67580, SR 48968 and SR 142801, respectively). 2. Microinjection of capsaicin reduced respiratory frequency but not tidal volume (VT), leading to an overall reduction in minute ventilation (VE). The effect was dose-dependent between 0.5 and 2 nmol capsaicin. Doses greater than 2 nmol produced apnoea. Tachyphylaxis was observed following repeated injection of capsaicin (1 nmol, 30 min apart). 3. Capsazepine (1 nmol) had no effect on frequency or VT when injected alone but completely blocked the respiratory response to capsaicin (1 nmol). 4. RP 67580 (1 but not 5 nmol) alone depressed frequency and VT slightly. Moreover, RP 67580 appeared to potentiate the bradypnoeic effect of capsaicin. In contrast, SR 48968 and SR 142801 (1 and 5 nmol) alone had no significant effect on respiration. However, both agents significantly attenuated the reduction in frequency produced by capsaicin. 5. In conclusion, microinjection of capsaicin into the cNTS decreases overall ventilation, primarily by reducing frequency. The action of capsaicin appears from the data to be mediated by vanilloid receptors since it is blocked by the competitive vanilloid antagonist capsazepine and is subject to tachyphylaxis. However, since NK2 (SR 48968) and NK3 (SR 142801) receptor antagonists block the actions of capsaicin, we propose that capsaicin acts also by releasing tachykinins from central afferent terminals in the cNTS.

MeSH Terms
Anesthesia Animals Benzamides/pharmacology Capsaicin/administration & dosage,analogs & derivatives,antagonists & inhibitors,pharmacology Dose-Response Relationship, Drug Indoles/pharmacology Isoindoles Male Microinjections Neurokinin-1 Receptor Antagonists Piperidines/pharmacology Rats Rats, Wistar Receptors, Drug/antagonists & inhibitors,drug effects Receptors, Neurokinin-2/antagonists & inhibitors Receptors, Neurokinin-3/antagonists & inhibitors Receptors, Tachykinin/antagonists & inhibitors,drug effects Respiratory Mechanics/drug effects Solitary Nucleus/cytology,drug effects Tidal Volume/drug effects
Chemicals
Benzamides Indoles Isoindoles Neurokinin-1 Receptor Antagonists Piperidines Receptors, Drug Receptors, Neurokinin-2 Receptors, Neurokinin-3 Receptors, Tachykinin 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one SR 48968 SR 142801 capsazepine Capsaicin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mazzone S B
School of Biomedical Science, University of Tasmania, Launceston, Australia.
Geraghty D P
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0702522
Published
1999-05-00
Pages
473-81
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1566015
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0702522 PMC Full Text View journal details
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