Inhibition of eicosanoid formation in human polymorphonuclear leukocytes by high concentrations of magnesium ions.
The cutaneous antiinflammatory action of Dead-Sea brine is thought to be due to magnesium ions. To elucidate their mode of action, we studied the influence of isotonic solutions containing high concentrations of Mg2+ (up to 115mM) on the formation of 5-lipoxygenase-derived eicosanoids in human polymorphonuclear leukocytes. The cells were stimulated by either ionophore A23187 or the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. We observed a pronounced inhibition of the formation of leukotriene B4 and 5-hydroxyeicosatetraenoic acid from either added [1-14C] or endogenously liberated arachidonic acid. In the latter case, the sum of arachidonic acid and its oxygenation products was also markedly diminished. The inhibitory effects of Mg2+ depended in a reciprocal manner on the concentration of Ca2+ in the incubation medium. An unspecific damage to cells as reason for the inhibitory effects was excluded. Human recombinant 5-lipoxygenase was also inhibited by Mg2+ in the same concentration range (IC50 16 mM). These data suggest that high concentrations of Mg2+ inhibit the eicosanoid metabolism both at the level of the liberation of arachidonic acid and by direct inhibition of the 5-lipoxygenase enzyme.
Ludwig
P
P
Institute of Biochemistry, Humboldt University of Berlin, Germany.
Petrich
K
K
Schewe
T
T
Diezel
W
W
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D015777:Eicosanoids; D005227:Fatty Acids; D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; D016859:Lipoxygenase Inhibitors; D011994:Recombinant Proteins; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001094:Arachidonate 5-Lipoxygenase; D008274:Magnesium; D002118:Calcium