Distribution of cytochrome p450 activities towards alkoxyresorufin derivatives in rat brain regions, subcellular fractions and isolated cerebral microvessels

doi:10.1016/0006-2952(90)90247-I

Biochemical Pharmacology

Volume 40, Issue 9, 1 November 1990, Pages 2145-2151

https://doi.org/10.1016/0006-2952(90)90247-I Get rights and content

Abstract

The regional and subcellular distributions of rat brain cytochrome P450 and cytochrome P450-dependent activities were examined. Cytochrome P450 was found to be mainly localized in mitochondria in all the six cerebral regions studied. The activities of the isoforms mostly implicated in drug metabolism, cytochromes P450 b and c, were measured by the dealkylation of two alkoxyresorufins, that are sensitive probe substrates for these isoforms. These activities have been measured in microsomal and mitochondrial fractions obtained from six different regions in male rat brains, as well as in microvessels. Resorufin derivatives dealkylation specific activities were higher in brain microsomal fractions than in hepatic ones in all the six regions examined when results were expressed per cytochrome P450 content. These brain microsomal specific activities were also higher than in mitochondrial fractions. Olfactory bulbs showed the highest cytochrome P450 content and activities in both microsomal and mitochondrial fractions. A sex-linked difference in cytochrome P450-dependent activities was also found. After anin vivo inducing pretreatment of rats, only 3-methylcholanthrene induced ethoxyresorufin O-deethylase activity, in the three preparations studied. These results provided (i) direct evidence that cytochromes P450 b and c isoforms are active in brain microsomal fractions, with regional and sexlinked differences, and (ii) the first demonstration of cytochrome P450-dependent activities in isolated rat brain microvessels.

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^☆: A preliminary report of this paper has been presented at the VIIth International Symposium on Microsomes and Drug Oxidations, June 25–29 1990, Stockholm, Sweden.

^†: R. Perrin is a recipient of a France-Parkinson Foundation fellowship.

^‡: To whom all cprrespondence should be addressed.

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Distribution of cytochrome p450 activities towards alkoxyresorufin derivatives in rat brain regions, subcellular fractions and isolated cerebral microvessels☆

Abstract

Biochem Pharmacol

Biochem Pharmacol

Biochem Biophys Res Commun

Biochem Biophys Res Commun

Biochem Pharmacol

Brain Res

Arch Biochem Biophys

Arch Biochem Biophys

Neurosci Lett

Life Sci

Neuroscience

Toxicol in Vitro

Biochem Pharmacol

N Neurosci Methods

Brain Res

Anal Biochem

J Biol Chem