Long-lasting agonist activity produced by a capsaicin-like photoaffinity probe

IF James, CS Walpole, J Hixon, JN Wood and R Wrigglesworth

Sandoz Institute for Medical Research, London, England.

Capsaicin causes uptake of 45Ca2+ into a subset of neurons cultured from rat dorsal root ganglia. One aryl azido analogue of capsaicin produced a long-lasting stimulation of calcium uptake after irradiation in contact with cells, but not if samples were kept in the dark. The active compound, like capsaicin, is a 3-methoxy, 4-hydroxy benzylamide. An analogue without substitutions on the benzyl ring and one without the ring were not agonists. This pattern is consistent with known structure-activity relationships for capsaicin analogues. All three aryl azides produced long-lasting inhibition of capsaicin action, which was not totally dependent on irradiation. Long lasting agonist action was not produced if reversible capsaicin agonists were present as protecting ligands during the irradiation step. Potency as protectors correlated well with potency as agonists in the calcium uptake assay. We suggest that the active aryl azide is a photoaffinity label for a specific capsaicin receptor on dorsal root ganglion neurons but the inhibitory effects are not dependent on binding to the receptor.

Volume 33, Issue 6, pp. 643-649, 06/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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