Competitive inhibition by capsazepine of [3H]resiniferatoxin binding to central (spinal cord and dorsal root ganglia) and peripheral (urinary bladder and airways) vanilloid (capsaicin) receptors in the rat.

Capsazepine was reported to block capsaicin- and resiniferatoxin (RTX)-induced responses both in vivo and in vitro with Schild plots suggesting a competitive mechanism of action. We have used the [3H]RTX binding assay, thought to represent the vanilloid (capsaicin) receptor, to explore the inhibitory mechanism of capsazepine at the receptor level in the rat. In competition assays, capsazepine inhibited [3H]RTX binding by spinal cord, dorsal root ganglion (DRG) and urinary bladder membranes with similar Ki values of 4.0 +/- 0.3, 3.5 +/- 0.5 and 5.0 +/- 1.0 microM (mean +/- S.E.M.; three determinations), respectively. By contrast, capsazepine was 35- to 50-fold more potent for inhibiting specific [3H]RTX binding in the airways (Ki = 0.12 +/- 0.02 microM; mean +/- S.E.M.; four determinations). In experiments in which the concentration of [3H]RTX was varied, 10 microM capsazepine reduced the affinity of the vanilloid receptor expressed by DRG and spinal cord membranes for [3H]RTX from 15 +/- 3 to 43 +/- 5 pM, and from 20 +/- 3 to 80 +/- 5 pM (mean +/- S.E.M.; three determinations), respectively, without a measurable change in Bmax or in cooperativity index; these shifts in affinity yield Ki values of 5.2 and 3.3 microM for DRG and spinal cord membranes, respectively. Capsaicin inhibited [3H]RTX binding by spinal cord, DRG and urinary bladder membranes with a 6- to 13-fold higher potency than did capsazepine; the Ki values were 0.3 +/- 0.1, 0.6 +/- 0.4 and 0.5 +/- 0.2 microM (mean +/- S.E.M.; three determinations), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)