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

Citation

Griffiths, CD and Eldershaw, TPD and Geraghty, DP and Hall, JL and Colquhoun, EQ, Capsaicin-induced biphasic oxygen uptake in rat muscle: antagonism by capsazepine and ruthenium red provides further evidence for peripheral vanilloid receptor subtypes (VN1/VN2), Life Sciences, 59, (2) pp. 105-117. ISSN 0024-3205 (1996) [Refereed Article]

DOI: doi:10.1016/0024-3205(96)00267-6

Abstract

Previous studies with the vanilloid spice principle capsaicin have demonstrated a biphasic VO 2 response, with vasoconstriction, in the perfused rat hindlimb that has led to suggestions of vanilloid receptor subtypes (VN 1/VN 2) 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 VO 2 produced by the putative VN 1 receptor at submicromolar concentrations of capsaicin, while the inhibition of VO 2 produced by high concentrations of capsaicin (putative VN 2) 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 K(B) = 8.44 ± 2.08 μM and 7.28 ± 0.78 μM for VO 2 and perfusion pressure curves, respectively). Low concentrations of the capsaicin antagonist ruthenium red selectively blocked the putative VN 2 receptor-mediated effects produced by high concentrations of capsaicin. The noncompetitive 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Basic Pharmacology
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Griffiths, CD (Mr Griffiths)
Author:Eldershaw, TPD (Mr Tristram Eldershaw)
Author:Geraghty, DP (Professor Dominic Geraghty)
Author:Hall, JL (Ms Jenny Hall)
Author:Colquhoun, EQ (Dr Eric Colquhoun)
ID Code:7418
Year Published:1996
Web of Science® Times Cited:25
Deposited By:Health Sciences A
Deposited On:1996-08-01
Last Modified:2011-08-19
Downloads:0

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