Pharmacological characterization of the vanilloid receptor in the rat dorsal 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 spinal 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 pEC50 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 receptor antagonist, capsazepine (10 microM) had no effect on basal peptide release but inhibited the CGRP release evoked by all 3 agonists to a similar extent. These results suggest that the antagonistic effects of capsazepine were agonist-independent. 4. The capsaicin-sensitive cation channel blocker, ruthenium red (10 microM) had no effect on basal CGRP release, but antagonized the peptide release evoked by capsaicin, olvanil and RTX. 5. The pharmacology of the vanilloid receptor in the rat dorsal spinal cord is not identical to that previously found in other systems. The reason for these differences is unclear, but the possibility of multiple classes of receptor cannot at this stage be ruled out.
Wardle
K A
KA
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow.
Ranson
J
J
Sanger
G J
GJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D009498:Neurotoxins; D011955:Receptors, Drug; C054256:olvanil; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin