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Regulation of heme and drug metabolism activities in the brain by manganese


Biochemical & Biophysical Research Communications 128(1): 18-24
Regulation of heme and drug metabolism activities in the brain by manganese
A novel effect of metal ions in the [rat] brain is described. Mn altered heme metabolism and the cytochrome P-450-dependent mixed-function oxidase activities in rat brain. A more than 2-fold increase in benzo(.alpha.)pyrene hydroxylase and 7-ethoxycoumarin deethylase activities were observed in the brain of rats treated for 7 days with Mn. The increases were regionally distributed; the highest elevations were observed in the hippocampus, pons and the caudate putamen. Moreover, in rats treated with Mn for 1 or 7 days a marked depression in the activity of the mitochondrial .delta.-aminolevulinate synthetase was observed. The activity of the microsomal heme oxygenase was also inhibited at 7 days, but not 1 day, after Mn treatment. These inhibitions were reflected in an initial decrease, followed by a rebound return to normal, in the concentration of cytochrome P-450 in the brain. Mn was ineffective in vitro in altering heme and drug metabolism activities. Mn-mediated alterations in heme matabolic activities may promote changes in the composition of cytochrome P-450 species in the brain microsomal fractions, such that the relative concentrations of the molecular species which catalyze aryl hydrocarbon hydroxylase activity become selectively increased.

Accession: 006288337

PMID: 3921022

DOI: 10.1016/0006-291x(85)91638-9

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