In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes
| Autor: | Nishioka Mikio, Orishiki Mitsuru, Ichikawa Yoshiyuki, Matsuo Yoshinori |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Oxidoreductases O-Demethylating Blotting Western 7-Alkoxycoumarin O-Dealkylase Pharmacology Ranitidine Biochemistry Isozyme Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System In vivo medicine Animals Rats Wistar Cimetidine Bufuralol Oxidoreductases N-Demethylating Monooxygenase Rats Cytochrome P-450 CYP2D6 chemistry Debrisoquine Microsomes Liver Benzphetamine Injections Intraperitoneal Aminopyrine N-Demethylase medicine.drug |
| Zdroj: | International Journal of Biochemistry. 26:751-758 |
| ISSN: | 0020-711X |
| Popis: | 1. 1. The effects of in vivo administration of H 2 blockers, cimetidine and ranitidine (0.6 mmol/kg body weight/day, for 5 days), on several P 450 isozymes, the P 450IID (CYP2D) subfamily, and their monooxygenase activities in rat liver microsomes were investigated. 2. 2. In vivo administration of cimetidine and ranitidine decreased the contents of P 450 isozymes and the activities of P 450-linked monooxygenase systems; i.e., benzphetamine N -demethylase, aminopyrine N -demethylase, 7-ethoxycoumarine O -deethylase, debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase. 3. 3. The inhibitory effect on the enzymatic activities of the P 450IID (CYP2D)-linked monooxygenase systems was studied by Western blot analysis with serum containing antiCYP2D6 IgG, i.e., LKM1 autoantibody. The amount of P 450IID (CYP2D) in liver microsomes decreased more remarkably in the group administered ranitidine or cimetidine in vivo than in controls. 4. 4. The effects of cimetidine and ranitidine on the activities of the P 450IID (CYP2D)-linked monooxygenase systems were investigated in vitro . The activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase were inhibited in vitro by cimetidine or ranitidine at a higher concentration than that on in vivo administration of either H 2 blocker. 5. 5. The kinetic parameters for cimetidine or ranitidine as to the activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase in liver microsomes were determined by means of Lineweaver-Burk plots. 6. 6. The suppressive effects of cimetidine and ranitidine on the activities of the P 450IID (CYP2D)-linked monooxygenase systems in vivo were found to be due to a decrease of the content of the P 450IID (CYP2D) protein. |
| Databáze: | OpenAIRE |
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