PHARMACOLOGICAL CHARACTERIZATION OF THE VANILLOID RECEPTOR IN THE RATDORSAL SPINAL-CORD

1 In the present study a novel 96-well plate assay system was used to characterize pharmacologically the vanilloid receptor in the dorsal sp inal cord of the rat. When activated, this receptor stimulates release of calcitonin gene-related peptide (CGRP) from the central terminals of the afferent nerves. 2 Capsaicin, resiniferatoxin (RTX) and olvanil each evoked a concentration-dependent increase in CGRP release with p EC(50) values of 6.55+/-0.07, 7.90+/-0.24 and 6.19+/-0.15 respectively . RTX and olvanil were partial agonists with respect to capsaicin. All concentration-effect curves were bell-shaped. 3 The vanilloid recepto r antagonist, capsazepine (10 mu M) had no effect on basal peptide rel ease but inhibited the CGRP release evoked by all 3 agonists to a simi lar extent. These results suggest that the antagonistic effects of cap sazepine were agonist-independent. 4 The capsaicin-sensitive cation ch annel blocker, ruthenium red (10 mu M) had no effect on basal CGRP rel ease, but antagonized the peptide release evoked by capsaicin, olvanil and RTX. 5 The pharmacology of the vanilloid receptor in the rat dors al spinal cord is not identical to that previously found in other syst ems. The reason for these differences is unclear, but the possibility of multiple classes of receptor cannot at this stage be ruled out.