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Paxilline

: The mycotoxin paxilline inhibits the cerebellar inositol 1,4, 5-trisphosphate receptor.; Longland CL, Dyer JL, Michelangeli F.

School of Biosciences, University of Birmingham, Edgbaston, B152TT, Birmingham, UK.

Paxilline, a tremorgenic alkaloid mycotoxin produced by Penicillium paxilline, is a reversible inhibitor of the cerebellar inositol 1,4, 5-trisphophate (InsP(3)) receptor. It inhibits the amount or extent of InsP(3)-induced Ca(2+) release (IICR), at sub-maximal concentrations of InsP(3), in a biphasic manner consistent with two inhibition constants (K(i)'s 6.7 and > or =400 microM). As paxilline does not affect InsP(3) binding to the receptor, it can be considered a non-competitive inhibitor. The fact that IICR is biphasic has been interpreted as there being two populations of InsP(3)-sensitive Ca(2+) stores, which release Ca(2+) in either a fast or slow fashion. This study has shown that the rate constants for Ca(2+) release from both the fast and slow populations are reduced by paxilline (100 microM) by about 70% and 60%, respectively. Detailed analysis of the way different concentrations of paxilline inhibit the rate constants for Ca(2+) release indicates that the population of Ca(2+) stores that contribute to the slower phase of Ca(2+) release is more sensitive to the inhibitory action of paxilline.

PMID: 11090637 [PubMed - indexed for MEDLINE]


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The mycotoxin paxilline inhibits the cerebellar inositol 1,4, 5-trisphosphate receptor.