Inflammation and inducible nitric oxide synthase have no effect on monoamine oxidase activity in glioma cells.

Heightened monoamine oxidase (MAO) and inducible nitric oxide synthase (iNOS) activity can contribute to oxidative stress, the formation of active neurotoxins, and associated neurodegenerative diseases of the brain. Although these enzymes co-exist within astrocytes, there has been little research examining the correlation between the two during inflammation. In this study, C6 glioma cells were stimulated with lipopolysaccharide (LPS):Escherichia coli 0111:B4 (6 micro g/mL):rat interferon-gamma (IFN-gamma) (100U/mL). In LPS/IFN-gamma-treated cells, the MAO substrates dopamine (DA) and tyramine caused a concentration-dependent attenuation of NO(2)(-) and NO(3)(-). In contrast, treatment with an MAO-A inhibitor (clorgyline) or an MAO-B inhibitor ((-)-deprenyl) did not reverse these effects. MAO activity was inhibited effectively by clorgyline and deprenyl; however, neither MAO inhibitor had an effect on NO(2)(-) in stimulated cells. Inversely, increasing concentrations of LPS/IFN-gamma resulted in heightened iNOS protein expression and NO(2)(-); however, these events did not correlate with any distinctive change in MAO enzyme activity. Moreover, a selective iNOS inhibitor, N(6)-(1-iminoethyl)-L-lysine, in LPS/IFN-gamma-stimulated cells caused a concentration-dependent attenuation of NO(2)(-) with no effects on MAO activity or iNOS protein expression. The attenuating effects of DA on iNOS were blocked completely by ICI 118-551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], indicating a role for the beta(2)-adrenergic receptor. In conclusion, these data indicate that activity or expression of iNOS does not influence MAO activity in activated rat glioma cells. Moreover, DA exerts an inhibitory effect on glial iNOS through a receptor-mediated cascade.