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• W2023486326 abstract "Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, capsaicin. The present study shows the capsazepine acts as a competitive antagonist of capsaicin. Capsazepine (10 μ m ) reversibly reduced or abolished the current response to capsaicin (500 n m ) of voltage‐clamped dorsal root ganglion (DRG) neurones from rats. In contrast, the responses to 50 μ m γ‐aminobutyric acid (GABA) and 5 μ m adenosine 5′‐triphosphate (ATP) were unaffected. The effects of capsazepine were examined quantitatively with radioactive ion flux experiments. Capsazepine inhibited the capsaicin (500 n m )‐induced 45 Ca 2+ uptake in cultures of rat DRG neurones with an IC 50 of 420 ± 46 n m (mean ± s.e.mean, n = 6). The 45 Ca 2+ uptake evoked by resiniferatoxin (RTX), a potent capsaicin‐like agonist was also inhibited. (Log concentration)‐effect curves for RTX (0.3 n m ‐1 μ m ) were shifted in a competitive manner by capsazepine. The Schild plot of the data had a slope of 1.08 ± 0.15 (s.e.) and gave an apparent K d estimate for capsazepine of 220 n m (95% confidence limits, 57–400 n m ). Capsazepine also inhibited the capsaicin‐ and RTX‐evoked efflux of 86 Rb + from cultured DRG neurones. The inhibition appeared to be competitive and Schild plots yielded apparent K d estimates of 148 n m (95% confidence limits, 30–332 n m ) with capsaicin as the agonist and 107 n m (95% confidence limits, 49–162 n m ) with RTX as agonist. A similar competitive inhibition by capsazepine was seen for capsaicin‐induced [ 14 C]‐guanidinium efflux from segments of adult rat vagus nerves (apparent K d = 690 n m ; 95% confidence limits, 63 n m ‐1.45 μ m ). No significant difference was noted in the apparent K d estimates for capsazepine in assays on cultured DRG neurones and vagus nerve as shown by the overlap in the 95% confidence limits. 6 Capsazepine, at concentrations up to 10 μ m , had no significant effects on the efflux of 86 Rb + from cultured DRG neurones evoked either by depolarization with high (50 m m ) K + solutions or by acidification of the external medium to pH 5.0–5.6. Similarly capsazepine had no significant effect on the depolarization (50 m m KCl)‐induced efflux of [ 14 C]‐guanidinium from vagus nerve preparations. 7 Ruthenium Red was also tested for antagonism against capsaicin evoked [ 14 C]‐guanidinium release from vague nerves and capsaicin induced 45 Ca 2+ uptake in cultures of DRG neurones. In contrast to capsazepine the inhibition by Ruthenium Red (10–500 n m in DRG and 0.5–10 μ m in vagus nerve experiments) was not consistent with a competitive antagonism, but rather suggested a more complex, non‐competitive inhibition." @default.
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• W2023486326 date "1992-10-01" @default.
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• W2023486326 title "Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin" @default.
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• W2023486326 doi "https://doi.org/10.1111/j.1476-5381.1992.tb12781.x" @default.
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