title: Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-450 2B and 3A forms.
abstract: 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.
authors.affiliation: Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Zangar
authors.forename: J R
authors.initials: JR
authors.lastname: Okita
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: P E
authors.initials: PE
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Anderson
authors.forename: R J
authors.initials: RJ
authors.lastname: Edwards
authors.forename: D L
authors.initials: DL
authors.lastname: Springer
authors.forename: R T
authors.initials: RT
authors.lastname: Okita
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000096:biosynthesis
chemical_list: D002121:Calcium Channel Blockers; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D009529:Nicardipine; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C089142:Cyp2b3 protein, rat; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; C025619:steroid 16-beta-hydroxylase; D010089:Oxidoreductases, N-Demethylating; D009543:Nifedipine