Magnolol induces cytosolic-free Ca2+ elevation in rat neutrophils primarily via inositol trisphosphate signalling pathway

Eur J Pharmacol. 1998 Jul 10;352(2-3):329-34. doi: 10.1016/s0014-2999(98)00363-x.

Abstract

In the present study, we describe the role of inositol trisphosphate in the signalling pathway that leads to the elevation of cytosolic-free Ca2+ in rat neutrophils stimulated with magnolol, a compound isolated from the cortex of Magnolia officinalis. Magnolol increased [Ca2+]i, by stimulating Ca2+ release from internal stores and Ca2+ influx across the plasma membrane, in a concentration-dependent manner. Ni2+ and [6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H -pyrrole-2,5-dione (U73122), but not pertussis toxin, inhibited the magnolol-induced Ca2+ influx. Measurement of cellular levels of inositol trisphosphate showed a clear increase upon exposure to magnolol. U73122 but not ryanodine suppressed the Ca2+ release from internal stores caused by magnolol. Pretreatment of cells with formyl-Met-Leu-Phe (fMLP) or cyclopiazonic acid greatly reduced the [Ca2+]i changes caused by the subsequent addition of magnolol. Collectively, these findings suggest that a pertussis toxin-insensitive inositol trisphosphate signalling pathway is involved in the magnolol-induced [Ca2+]i elevation in rat neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / pharmacology*
  • Calcium / metabolism*
  • Cytosol / metabolism*
  • Estrenes / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Lignans*
  • Manganese / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Pyrrolidinones / pharmacology
  • Rats
  • Ryanodine / pharmacology
  • Signal Transduction / drug effects*

Substances

  • Biphenyl Compounds
  • Estrenes
  • Indoles
  • Lignans
  • Pyrrolidinones
  • magnolol
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Ryanodine
  • Manganese
  • N-Formylmethionine Leucyl-Phenylalanine
  • Inositol 1,4,5-Trisphosphate
  • Calcium
  • cyclopiazonic acid