Magnolol induces cytosolic-free Ca2+ elevation in rat neutrophils primarily via inositol trisphosphate signalling pathway.
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.
Department of Medical Research, Taichung Veterans General Hospital, Taiwan.
J P
JP
Wang
C C
CC
Chen
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D017705:Lignans; D008345:Manganese / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D001713:Biphenyl Compounds; D004963:Estrenes; D007211:Indoles; D017705:Lignans; D011760:Pyrrolidinones; C005498:magnolol; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D008345:Manganese; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; C000543:cyclopiazonic acid