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Titolo:
High-performance liquid chromatographic analysis of the sulfation of 4-hydroxypropranolol enantiomers by monkey liver cytosol
Autore:
Narimatsu, S; Kobayashi, N; Asaoka, K; Masubuchi, Y; Horie, T; Hosokawa, M; Ishikawa, T; Ohmori, S; Kitada, M; Miyano, J; Kataoka, H; Yamamoto, S;
Indirizzi:
Okayama Univ, Fac Pharmaceut Sci, Lab Hlth Chem, Okayama 7008530, Japan Okayama Univ Okayama Japan 7008530 Lab Hlth Chem, Okayama 7008530, Japan Chiba Univ, Fac Pharmaceut Sci, Lab Biopharmaceut, Chiba 260, Japan Chiba Univ Chiba Japan 260 ceut Sci, Lab Biopharmaceut, Chiba 260, Japan Kyoto Univ, Primate Res Inst, Dept Cellular & Mol Biol, Aichi, Japan KyotoUniv Aichi Japan Res Inst, Dept Cellular & Mol Biol, Aichi, Japan Chiba Univ, Fac Pharmaceut Sci, Biochem Pharmacol Lab, Chiba 260, Japan Chiba Univ Chiba Japan 260 Sci, Biochem Pharmacol Lab, Chiba 260, Japan Chiba Univ, Fac Pharmaceut Sci, Lab Med Organ Chem, Chiba 260, Japan ChibaUniv Chiba Japan 260 eut Sci, Lab Med Organ Chem, Chiba 260, Japan Chiba Univ Hosp, Sch Med, Div Pharm, Chiba, Japan Chiba Univ Hosp Chiba Japan Univ Hosp, Sch Med, Div Pharm, Chiba, Japan
Titolo Testata:
CHIRALITY
fascicolo: 3, volume: 13, anno: 2001,
pagine: 140 - 147
SICI:
0899-0042(2001)13:3<140:HLCAOT>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-LIVER; PROPRANOLOL METABOLISM; MICROSOMAL PROTEINS; COVALENT BINDING; CONJUGATION; SUBFAMILY;
Keywords:
4-hydroxypropranolol; sulfate enantiomer; HPLC; human and monkey liver cytosol; kinetics; enantioselectivity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Narimatsu, S Okayama Univ, Fac Pharmaceut Sci, Lab Hlth Chem, 1-1-1 Tsushima Naka, Okayama 7008530, Japan Okayama Univ 1-1-1 Tsushima Naka Okayama Japan 7008530 Japan
Citazione:
S. Narimatsu et al., "High-performance liquid chromatographic analysis of the sulfation of 4-hydroxypropranolol enantiomers by monkey liver cytosol", CHIRALITY, 13(3), 2001, pp. 140-147

Abstract

We developed a new high-performance liquid chromatographic method using anODS column and a chiral column for the assay of racemic 4-OH-PL sulfate and enantiomeric 4-OH-PL sulfates, respectively. The method was successfully applied to measure phenolsulfotransferase (PST) activities for 4-OH-PL in cytosolic fractions from livers of Japanese monkeys (Macaca fuscata) and forcomparison with its activity of cytosolic fractions from rat, rabbit, dog,and human livers and Hep G2 cells. The activity was ranked as Hep G2 cells> monkeys = humans = dogs = rats > rabbits. To evaluate the Japanese monkey as a nonhuman animal model in drug metabolism studies, we further characterized sulfation of 4-OH-PL as a further metabolic pathway in monkey liversto compare that with human livers. Inhibition studies in which cytosolic fractions were preincubated at 43 degreesC or 2,6-dichloro-4-nitrophenol (DCNP) used as a PST inhibitor indicated that two kinds of PSTs, thermolabile,low-Km and DCNP-resistant PST and thermostable, high-Km and DCNP-sensitivePST were involved in 4-OH-PL sulfation by monkey liver cytosol, which is very similar to the reported profile of COH-PL sulfation by human liver cytosol. Sulfation kinetics in a low concentration range of 4-OH-PL enantiomersdemonstrated that apparent Km values were similar between human and monkeyliver cytosolic fractions, but the Vmax values were different, so that intrinsic clearance values (Vmax/Km, CLint) were higher in monkeys than in humans. Furthermore, enantiomer selectivity of [R(+)-4-OH-PL > S(-)-4-OH-PL] was observed in the Vmax and CLint values of monkey liver cytosol. These results indicate that the profile of sulfation of 4-OH-PL by liver cytosolic fractions is similar in humans and Japanese monkeys. Chirality 13:140-147, 2001. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 20:06:18