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Xenobiotica
the fate of foreign compounds in biological systems
Volume 25, 1995 - Issue 8
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Research Article

Induction of hepatic microsomal P450 by 4-phenylalkylpyridines in rat: chain length-dependent and sex-related differential induction of P450s

Y. Kobayashi Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
,
T. Yoshida Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142, Japan
,
E. Kotani Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
,
Y. Matsuura Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
,
H. Egawa Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
,
T. Aoyagi Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
,
S. Imaoka Laboratory of Chemistry, Osaka City University Medical School, 1-4-54, Asahimachi, Abeno-ku, Osaka, 545, Japan
,
Y. Funae Laboratory of Chemistry, Osaka City University Medical School, 1-4-54, Asahimachi, Abeno-ku, Osaka, 545, Japan
,
S. Tobinaga Showa College of Pharmaceutical Sciences, 3165, 3-chome, Higashitamagawagakuen, Machida-shi, Tokyo, 194, Japan
&
Y. Kuroiwa Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142, Japan
 show all
Pages 779-789 | Received 23 Jan 1995, Published online: 22 Sep 2008
 
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Abstract

1. The effects of 4-phenylalkylpyridines (chain length of 0-5, 7, 9 and 11 carbon atoms) on the induction of hepatic microsomal P450 and its multiple forms (1A1/2 (1A1, 1A2), 3A2, 2B1/2, 2C6 and 2E1) in the male and female rat have been investigated.

2. P450 induction gradually declined with increasing chain length of the 4-phenylalkylpyridines.

3. Immunoblot analysis revealed that three pyridine compounds having methylene units of 0, 1 and 2 only induced P4501A2, whereas those having 4, 5 or 7 methylene units only induced 1A1 in the male rat.

4. In the female rat, however, we could not observe such a chain length-dependent differential induction of the P4501A subfamily.

5. Induced levels of P4503A2 and 2E1 were dependent on total P450 specific content, but 2C6 was increased in a chain length-dependent manner in both sexes.

6. These results provide new information on the differential effects of pyridine-containing compounds on P450 induction in the rat.

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