INTERACTION OF PROSTAGLANDINS WITH ADRENAL MICROSOMAL CYTOCHROME-P-450 IN THE GUINEA-PIG

被引:13
作者
GREINER, JW
KRAMER, RE
COLBY, HD
机构
[1] Department of Physiology, Biophysics West Virginia University School of Medicine Morgantown
来源
PROSTAGLANDINS | 1979年 / 17卷 / 04期
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
D O I
10.1016/0090-6980(79)90010-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Studies were carried out to investigate the effects of prostaglandins (PG) in vitro on adrenal microsomal steroid and drug metabolism in the guinea pig. The addition of PGE1, PGE2, PGA1, PGF1α or PGF2α to isolated adrenal microsomes produced typical type I difference spectra. The sizes of the spectra (ΔA385-420) produced by prostaglandins were smaller than those produced by various steroids including progesterone, 17-hydroxyprogesterone and 11β-hydroxyprogesterone. However, the affinities of prostaglandins and steroids for adrenal microsomal cytochrome P-450, as estimated by the spectral dissociation constants, were similar. Prior addition of prostaglandins to isolated adrenal microsomes did not affect steroid binding to cytochrome P-450 or the rate of steroid 21-hydroxylation. In contrast, prostaglandins inhibited adrenal metabolism of ethylmorphine and diminished the magnitude of the ethylmorphine-induced spectral change in adrenal microsomes. The results indicate that prostaglandins inhibit adrenal drug metabolism by interfering with substrate binding to cytochrome P-450. Since 21-hydroxylation was unaffected by PG, different cytochrome P-450 moieties are probably involved in adrenal drug and steroid metabolism. © 1979.
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页码:587 / 597
页数:11
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