A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors

A. Szallasi, T. Bíró, T. Szabó, S. Modarres, M. Petersen, A. Klusch, P. M. Blumberg, J. E. Krause, O. Sterner

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

1. A [3H]-resiniferatoxin (RTX) binding assay utilizing rat spinal cord membranes was employed to identify novel vanilloids in a collection of natural products of fungal origin. Of the five active compounds found (scutigeral, acetyl-scutigeral, ovinal, neogrifolin, and methyl-neogrifolin), scutigeral (K(i) = 19 μM), isolated from the edible mushroom Albatrellus ovinus, was selected for further characterization. 2. Scutigeral induced a dose-dependent 45Ca uptake by rat dorsal root ganglion neurons with an EC50 of 1.6 μM, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine (IC50 = 5.2 μM). 3. [3H]-RTX binding isotherms were shifted by scutigeral (10-80 μM) in a competitive manner. The Schild plot of the data had a slope of 0.8 and gave an apparent K(d) estimate for scutigeral of 32 μM. 4. Although in the above assays scutigeral mimicked capsaicin, it was not pungent on the human tongue up to a dose of 100 nmol per tongue, nor did it provoke protective wiping movements in the rat (up to 100 μM) upon intraocular instillation. 5. In accord with being non-pungent, scutigeral (5 μM) did not elicit a measurable inward current in isolated rat dorsal root ganglion neurons under voltage-clamp conditions. It did, however, reduce the proportion of neurons (from 61 to 15%) that responded to a subsequent capsaicin (1 μM) challenge. In these neurons, scutigeral both delayed (from 27 to 72 s) and diminished (from 5.0 to 1.9 nA) the maximal current evoked by capsaicin. 6. In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids.

Original languageEnglish
Pages (from-to)1351-1358
Number of pages8
JournalBritish journal of pharmacology
Volume126
Issue number6
DOIs
Publication statusPublished - Jan 1 1999

Keywords

  • Capsaicin
  • Non-pungent vanilloids
  • Resiniferatoxin
  • Scutigeral
  • Triprenyl phenols
  • Vanilloid receptors

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors'. Together they form a unique fingerprint.

  • Cite this