+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Regioselective contribution of the cytochrome P-450 2D subfamily to propranolol metabolism in rat liver microsomes

Regioselective contribution of the cytochrome P-450 2D subfamily to propranolol metabolism in rat liver microsomes

Drug Metabolism and Disposition: the Biological Fate of Chemicals 21(6): 1012-1016

The metabolism of propranolol was examined by using microsomes from Dark Agouti rats known as a poor-metabolizer animal model for debrisoquine 4-hydroxylation and Wistar rats. Propranolol 4- and 5-hydroxylations followed biphasic Michaelis-Menten kinetics, and 7-hydroxylation and N-desisopropylation were monophasic in both strains. The kinetic studies showed that the V-max for propranolol 7-hydroxylase activity and the V-max of high-affinity phases for propranolol 4- and 5-hydroxylase activities were markedly low in Dark Agouti rats compared with those in Wistar rats. The antibody against a cytochrome P-450 isozyme, P-450BTL (Suzuki, T., et al., Drug Metab. Dispos. 20, 367-373, 1992), belonging to the CYP2D subfamily, inhibited by 90% propranolol 4-, 5-, and 7-hydroxylase activities in liver microsomes from male Wistar rats at a low propranolol concentration (5 mu-M). However, less inhibitory effects of the antibody on propranolol 4- and 5-hydroxylase activities were observed at a high propranolol concentration (1 mM), whereas a similar inhibitory effect of the antibody on propranolol 7-hydroxylase activity was shown. The antibody inhibited propranolol N-desisopropylase activity, but less extent of the inhibition on this activity than those on ring-hydroxylase activities was observed at the low and high propranolol concentrations. These results indicate that a polymorphic cytochrome P-450 isozyme(s) belonging to the CYP2D subfamily is involved predominantly in propranolol 4-, 5-, and 7-hydroxylations at low substrate concentrations in the rat.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 009318433

Download citation: RISBibTeXText

PMID: 7905378

Related references

Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochemical Pharmacology 48(1): 173-182, 1994

Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily. Drug Metabolism and Disposition: the Biological Fate of Chemicals 25(5): 623-630, 1997

Oxidative metabolism of monensin in rat liver microsomes and interactions with tiamulin and other chemotherapeutic agents: evidence for the involvement of cytochrome P-450 3A subfamily. Drug Metabolism and Disposition: the Biological Fate of Chemicals 27(9): 1039-1044, 1999

Cytochrome P450-catalyzed metabolism of the aminoflavone analog NSC 686288 in human and rat liver microsomes The role of CYP1A subfamily enzymes. Proceedings of the American Association for Cancer Research Annual Meeting 40: 384, 1999

Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes: The role of CYP2D6 as ring-hydroxylase and CYP1A3 as N-desisopropylase. Drug Metabolism & Disposition 22(6): 909-915, 1994

Relative contribution of various forms of cytochrome P450 to the metabolism of benzo[a]pyrene by human liver microsomes. Carcinogenesis 10(10): 1815-1821, 1989

Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes. Biomedical Chromatography 24(8): 868-877, 2010

Mechanism of alterations of non linearity in hepatic first pass metabolism of propranolol alterations in the relative abundance of cytochrome p 450 isozymes in the liver microsomes in relation to the organ level metabolic activities. Journal of Pharmacobio-Dynamics 13(4): S98, 1990

Spectral interaction of propranolol with cytochrome p 450 of rat liver microsomes. Federation Proceedings 36(3): 1031, 1977

Regioselective and stereoselective hydroxylations of warfarin in human liver microsomes and c-DNA expressed cytochrome P450. Drug Metabolism Reviews 32(Suppl. 1): 35, 2000

Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. European Journal of Biochemistry 200(2): 511-517, 1991

Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Archives of Biochemistry and Biophysics 320(2): 380-389, 1995