Details

Autor(en) / Beteiligte

• Pastrakuljic, Aleksandra
• Tang, Bing K.
• Roberts, Eve A.
• Kalow, Wemer

Titel

Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole

Ist Teil von

• Biochemical pharmacology, 1997-02, Vol.53 (4), p.531-538

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1997

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Ethoxyresorufin O-deethylation (EROD) has been used as a specific probe for CYP1A1 and CYP1A2. Selective inhibition of one of these cytochromes P450 may differentiate their activity in human liver. Four inhibitors were chosen to examine the selective inhibition of EROD activity, using cDNA of CYP1A1 and CYP1A2. The two flavones, α-naphthoflavone and apigenin, while differing in potency, inhibited expressed human CYP1A1, CYP1A2, and human liver microsomes to a similar extent. Isosafrole and fluvoxamine were found to inhibit CYP1A2 selectively, with K i , values of 14 and 800 times, respectively, lower than those for CYP1A1. A set of equations was developed to estimate both CYP1A1 and CYP1A2 activity. Levels of CYP1A2 in four human liver specimens ranged from 44.4 to 76.7 pmol/mg protein, which significantly correlated with phenacetin O-deethylase activity ( gt = 0.99; P < 0.001). Low levels of CYP1A1 activity were present in all four investigated livers, ranging from 0.4 to 2.7 pmol/mg protein. BIOCHEM PHARMACOL 53;4:531–538, 1997. /sC 1997 Elsevier Science Inc.