Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-450 2B and 3A forms
| Autor: | R C, Zangar, J R, Okita, H, Kim, P E, Thomas, A, Anderson, R J, Edwards, D L, Springer, R T, Okita |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Nifedipine Blotting Western Oxidoreductases N-Demethylating Calcium Channel Blockers Rats Isoenzymes Rats Sprague-Dawley Nicardipine Cytochrome P-450 Enzyme System Liver Enzyme Induction Cytochrome P-450 CYP2B1 Steroid Hydroxylases Animals Cytochrome P-450 CYP3A Aryl Hydrocarbon Hydroxylases Cytochrome P450 Family 2 |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 290(3) |
| ISSN: | 0022-3565 |
| Popis: | Calcium channel antagonists are widely prescribed for treatment of hypertension. In this study, we examined whether treatment with the calcium channel antagonists, nicardipine, nifedipine or diltiazem, alters cytochrome P-450 2B or 3A (CYP2B or CYP3A, respectively) expression in rat liver. Western blot analyses were undertaken using antibodies specific for one or several members of these cytochrome P-450 subfamilies. Nicardipine was found to be an effective inducer of CYP3A; in particular, CYP3A23 was increased approximately 36-fold following treatment with 100 mg of nicardipine/kg/day. Nicardipine induced CYP2B forms up to approximately 3.1-fold. Nifedipine did not alter CYP3A expression but did increase CYP2B expression such that total CYP2B, CYP2B1, and CYP2B2v (a splice variant of CYP2B2) were increased approximately 5- to 15-fold after treatment with 100 mg of nifedipine/kg/day, with increases in benzyloxyresorufin O-dealkylase and erythromycin N-demethylase activities, respectively. The distinct differences in cytochrome P-450 induction profile induced by nicardipine and nifedipine suggest that they may enhance cytochrome P-450 expression by different mechanisms unrelated to their effects on calcium channels. |
| Databáze: | OpenAIRE |
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