Capsaicin-induced biphasic oxygen uptake in rat muscle: Antagonism by capsazepine and ruthenium red provides further evidence for peripheral vanilloid receptor subtypes (VN1/VN2)

Cory D. Griffiths, Tristram P.D. Eldershaw, Dominic P. Geraghty, Jennifer L. Hall, Eric Q. Colquhoun

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Previous studies with the vanilloid spice principle capsaicin have demonstrated a biphasic VO2 response, with vasoconstriction, in the perfused rat hindlimb that has led to suggestions of vanilloid receptor subtypes (VN1/VN2) in this preparation (1). In the present study, the known competitive vanilloid antagonist capsazepine inhibited the above capsaicin-mediated effects in a manner that was indicative of binding at specific vanilloid recognition sites. Low concentrations of capsazepine selectively inhibited the increased VO2 produced by the putative VN1 receptor at submicromolar concentrations of capsaicin, while the inhibition of VO2 produced by high concentrations of capsaicin (putative VN2) was enhanced. These observations, showing different susceptibilities to blockade by capsazepine, further support the presence of two vanilloid receptor subtypes in the rat hindlimb. Schild plots of the data yielded variable slopes that approach unity at greater responses to capsaicin (mean KB = 8.44 ± 2.08 μM and 7.28 ± 0.78 μM for VO2 and perfusion pressure curves, respectively). Low concentrations of the capsaicin antagonist ruthenium red selectively blocked the putative VN2 receptor-mediated effects produced by high concentrations of capsaicin. The non-competitive nature of this inhibitor suggests an operation through separate receptor-coupled ion channel complexes at high and low concentrations of the vanilloid. Tetrodotoxin failed to attenuate any changes produced by capsaicin, suggesting that the mechanism of action of capsaicin in the rat hindlimb may differ from other tissues.

Original languageEnglish (US)
Pages (from-to)105-117
Number of pages13
JournalLife Sciences
Volume59
Issue number2
DOIs
StatePublished - Jul 7 1996
Externally publishedYes

Keywords

  • Capsaicin
  • Capsazepine
  • Oxygen consumption
  • Receptor subtypes
  • Ruthenium red
  • Vasoconstriction

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