Curcumin: A new cell-permeant inhibitor of the inositol 1,4,5-triphosphate receptor

J. L. Dyer, S. Zafar Khan, J. G. Bilmen, S. R. Hawtin, M. Wheatley, M. Ul H. Javed, F. Michelangeli

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Curcumin (diferuoylmethane or 1,7-bis (4-hydroxy-3-methoxyphenol)-1,6-hepatadiene-3,5-dione) is the active ingredient of the spice turmeric. Curcumin has been shown to have a number of pharmacological and therapeutic uses. This study shows that curcumin is a potent inhibitor of the inositol 1,4,5-trisphosphate-sensitive Ca2+ channel (InsP3 receptor). In porcine cerebellar microsomes, the extent of InsP3-induced Ca2+ release (IICR) is almost completely inhibited by 50 μM curcumin (IC50=10μM). As the extent of IICR cannot be restored back to control levels by the addition of excess InsP3 and since it has little effect on [3H]InsP3 binding to cerebellar microsomes, this inhibition is likely to be non-competitive in nature. IICR in cerebellar microsomes is biphasic consisting of a fast and slow component. The rate constants for the two components are both reduced by curcumin to similar extents (by about 70% of control values at 40 μM curcumin). In addition, curcumin also reduces agonist (ATP)-stimulated Ca2+ mobilization from intact HL-60 cells, indicating that curcumin is cell permeant. However, since it also affects intracellular Ca2+ pumps and possibly ryanodine receptors, it may lead to complex Ca2+ transient responses within cells, which may well explain some of its putative therapeutic properties.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalCell Calcium
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2002
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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