title: Magnesium-deficient medium enhances NO production in alveolar macrophages isolated from rats.
abstract: Magnesium deficiency has been shown to increase nitric oxide (NO) levels in plasma and to aggravate endotoxin lethality. The present study was performed to examine the effects of magnesium (Mg(2+))-deficient culture medium, with and without endotoxin (LPS), on NO release and inducible NOS (iNOS) mRNA levels in alveolar macrophages isolated from rats. Decreasing the Mg(2+) concentration in the culture medium from 0.39 mM (normal-Mg(2+) medium) to 0.021 mM (Mg(2+)-deficient medium) increased NO release from alveolar macrophages for 2 h. However, LPS stimulation in Mg(2+)-deficient medium had little effect on NO release. The increased NO release in Mg(2+)-deficient medium was suppressed completely by L-NAME and aminoguanidine. Dexamethasone, pyrrolidine dithiocarbamate and curcumin strongly inhibited NO release. Verapamil, U73122, TMB-8 and W-7 had no significant effect on NO release induced by Mg(2+) deficiency. Preculture of macrophages with Mg(2+)-deficient medium for 22 h markedly increased NO release and iNOS mRNA levels for a further 2 h; these increments were suppressed completely by curcumin. These results suggest that Mg(2+) deficiency enhances NO production via iNOS by alveolar macrophages. In this experimental condition, we can not suggest that NO production from alveolar macrophage plays an essential role in the pathogenesis of enhanced endotoxin lethality in Mg-deficient rats.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Oono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Akira
authors.initials: A
authors.lastname: Nishio
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D003470:Culture Media; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats
chemical_list: D003470:Culture Media; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester