Induction of hepatic microsomal P450 by 4-phenylalkylpyridines in rat: chain length-dependent and sex-related differential induction of P450s.
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. P450 induction gradually declined with increasing chain length of the 4-phenylalkylpyridines. 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. In the female rat, however, we could not observe such a chain length-dependent differential induction of the P4501A subfamily. 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. These results provide new information on the differential effects of pyridine-containing compounds on P450 induction in the rat.
Kobayashi
Y
Y
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Yoshida
T
T
Kotani
E
E
Matsuura
Y
Y
Egawa
H
H
Aoyagi
T
T
Imaoka
S
S
Funae
Y
Y
Tobinaga
S
S
Kuroiwa
Y
Y
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D011725:Pyridines; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital