The Effects of H2-Receptor Antagonists and Imidazole on Testosterone Hydroxylations in Mouse Liver Microsomes

• Published in: Chemical & pharmaceutical bulletin Vol. 32; no. 10; pp. 4043 - 4048
• Main Authors: MORITA, KUNIHIKO, ONO, TAKESHI, SHIMAKAWA, HARUMI, WADA, FUMIO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1984; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Biological and medical sciences; Chromatography, Thin Layer - methods; Digestive system; Histamine H2 Antagonists - pharmacology; Hydroxylation; Imidazoles - pharmacology; Male; Medical sciences; Mice; Microsomes, Liver - metabolism; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet - methods; Testosterone - metabolism; TLC; Hydroxylation; Rat; Liver; Rodentia; Microsome; Ultraviolet spectrometry; Antihistaminic; In vitro; Thin layer chromatography; Testosterone; Vertebrata; Mammalia; H2 receptor
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.32.4043

A simple assay method for testosterone hydroxylase activity by thin-layer chromatographyultraviolet spectrophotometry was developed. By using this method, the effects of various H2-receptor antagonists (cimetidine, CIM ; metiamide, MET ; ranitidine, RAN ; famotidine, FAM) or imidazole (IMZ) on the hydroxylations of testosterone by mouse liver microsomal enzymes were studied in vitro. CIM and MET inhibited the 6β-, 7α-and 16α-hydroxylations in a dose-dependent manner. RAN and FAM had little inhibitory effect on any hydroxylation. IMZ inhibited the 6β-hydroxylation to the same degree as CIM and MET, while the effects on the 7α-and 16α-hydroxylations were very weak. The kinetic data indicated that these drugs inhibited the three hydroxylation reactions competitively and the affinities for each hydroxylase varied from drug to drug. The results suggest that the inhibitory actions of CIM or MET on the hydroxylations of testosterone are due to the imidazole ring structure, and the side chain structures may play a role in the enhancement of affinity to the enzymes, particularly the 7α-and 16α-hydroxylases. On the other hand, RAN and FAM containing a ring structure different from imidazole had little effect on any testosterone hydroxylase.