SEX AND STRAIN DIFFERENCES IN BASAL AND INDUCED ANILINE HYDROXYLASE AND ETHYLMORPHINE N-DEMETHYLASE ACTIVITIES FROM DOMESTIC AND WILD RATS

被引:28
作者
PAGE, JG
VESELL, ES
机构
[1] Section on Pharmacogenetics, Laboratory of Chemical Pharmacology, National Heart Institute, Bethesda, MD
关键词
D O I
10.1159/000136037
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Differences reaching approximately two-fold in the apparent Km and Vmax for ethylmorphine N-demethylase and aniline hydroxylase occurred in liver microsomes from eight inbred and two outbred strains of Raitus norvegicus. Most domestic strains exhibited quite similar values for these parameters. In five of the ten domestic strains males metabolized aniline from 0.1 to 2.0 times more rapidly than female rats, whereas no significant sex difference occurred in the other five strains. Sex differences with respect to ethylmorphine were approximately thiree-fold in all domestic strains. The apparent Km for ethylmorphine N-demethylase was higher in females than males of all but one of the domestic strains, whereas for aniline hydroxylase negligible sex differences occurred in seven of ten domestic strains and apparent Km values were slightly higher in males than in females of the remaining three strains. Wild Norwegian and kangaroo rats failed to exhibit significant sex differences in the metabolism of ethylmorphine or aniline. The variability of their values was much greater than that observed in domestic strains. Hepatic microsomes from wild Norwegian rats had ethylmorphine N-dcmethylase activities and cytochrome P-450 values approximately one-half those from domestic strains. Microsomal enzymes from male wild rats exhibited lower reactivity with ethylmorphine than did those from male domestic rats. With microsomes from wild Norwegian and kangaroo rats the apparent Km of aniline hydroxylase was significantly different from the apparent Km’s observed with microsomes from domestic strains; the apparent Km for ethylmorphine N-demethylase from wild rats did not differ significantly from that observed using domestic strains. In the 9,000 X g liver supernatant fraction from 10 domestic rat strains phenobarbital pretreatment elevated ethylmorphine and aniline metabolism approximately two to three fold in each strain, and tberc existed approximately two-fold differences among certain strains in the induced levels of these enzymes. Most domestic strains were very similar both in basal and induced activities of ethylmorphine N-de-methylase and aniline hydroxylase. © 1969 S. Karger AG, Basel.
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页码:321 / &
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