Cytochrome P-450 b and c in the rat brain and pituitary gland

BM Naslund, H Glaumann, M Warner, JA Gustafsson and T Hansson

Department of Medical Nutrition, Huddinge University Hospital, Sweden.

A quantitative assessment of the levels of cytochromes P-450 b and P- 450 c in the brains and pituitary glands of untreated and beta- naphthoflavone (BNF)-pretreated rats was made with polyclonal antibodies raised against hepatic P-450 b and c and the sensitive fluorometric assay of P-450 catalytic activity, namely, the O- deethylation of ethoxycoumarin (ETC). In the microsomal fraction of brains of untreated rats, the rate of formation of 7-hydroxycoumarin from ETC ranged between 0.1 and 20 pmol/min/mg of microsomal protein, which is approximately 0.01-2% of the level of hepatic microsomes of phenobarbital-induced rats. This brain activity was completely inhibited by anti P-450 b antibodies but was unaffected by anti P-450 c antibodies. As with hepatic P-450 b, metyrapone and chloramphenicol (100 microM) were good inhibitors of catalytic activity, whereas alpha- naphthoflavone (1 microM) was a poor inhibitor. No ETC O-deethylase activity was detectable in microsomes prepared from the pituitary glands of untreated rats. Upon pretreatment of rats with BNF, there was induction of ETC O-deethylase activity in the pituitary gland to a level of 3.3 +/- 1.5 pmol/min/mg of microsomal protein, but there was no significant increase in the level of activity in brain microsomes. Despite this, there was evidence of induction of P-450 c in both the brain and pituitary of BNF-pretreated rats since anti P-450 c antibodies inhibited brain activity by 55% and pituitary activity by 84%. The regional distribution of P-450 b and c in the hypothalamic- preoptic area and olfactory bulbs was examined. The level of ETC O- deethylase activity in the hypothalamic-preoptic area was not different from that in the whole brain, but in the olfactory bulbs activity was higher than that in whole brain, with a range of 0.1-52 pmol/min/mg of microsomal protein. The catalytic activity in the whole brain and in the olfactory bulbs was inhibited by anti P-450b but not by anti P-450c antibodies. Neither estradiol, testosterone, dehydrotestosterone, nor 5 alpha-androstane,3 beta,17 beta-diol (100 microM) competitively inhibited ETC O-deethylase activity, indicating that P-450 b is not responsible for the steroid hydroxylations previously reported in the brain. BNS pretreatment of rats did not cause a consistent increase in ETC O-deethylase upon BNF induction. However, there was an induction of P-450 c in the olfactory bulbs since catalytic activity was inhibited with anti P-450c antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Volume 33, Issue 1, pp. 31-37, 01/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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