A Novel Cytochrome P450 3A Isoenzyme in Rat Intestinal Microsomes

Gushchin, Ghennady V.; Gushchin, Marina I.; Gerber, Nicholas; Boyd, Ryan L.

doi:10.1006/bbrc.1999.0200

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…In this analysis, several bands were found at slightly different positions than CYP3A2. It has been shown that CYP3A1 and CYP3A2 are not expressed in rat intestine; and instead, the mainly expressed forms are CYP3A9, CYP3A18, and CYP3A62 (28,29). Although it was impossible to isolate these CYP3A isoforms in this study since we used a polyclonal CYP3A2 antibody, it seemed to crossreact with the other CYP3A isoforms and provided a band corresponding to the total CYP3As.…”

Section: Discussionmentioning

confidence: 82%

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Effects of Continuous Ingestion of Herbal Teas on Intestinal CYP3A in the Rat

et al. 2007

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Abstract. Tenryocha, rooibos, and guava teas are widely consumed as herbal beverages, especially as a therapy against pollen allergy. To investigate the possible herbal tea-drug interaction the effect of continuous ingestion of these teas on cytochrome P450 (CYP) 3A were studied. Rats (n = 6) were allowed free access to either tea (experimental groups) or water (control) for two weeks. Midazolam (MDZ) (20 mg / kg) was orally administered and the serum concentration was determined. The area under the serum concentration-time curve (AUC 0-∞ ) and the maximum serum concentrations (C max ) of MDZ were reduced by more than 60% after the treatment of tenryocha and rooibos tea (P<0.05). Intestinal MDZ 1'-and 4-hydroxylation activities mediated by CYP3A were increased in tenryocha and rooibos tea-treated group by 50% compared to the control group, although the results were not statistically significant. Furthermore, the Western blot analysis showed that CYP3A content was significantly increased in the intestine after the treatment of these teas (P<0.05). Hepatic MDZ hydroxylation and CYP3A content were slightly increased by these teas. The results suggested that two weeks ingestion of tenryocha and rooibos tea reduced serum concentration of MDZ by the induction of intestinal CYP3A. The possible interaction between tenryocha or rooibos tea and medicines mediated by CYP3A was suggested.

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Section: Discussionmentioning

confidence: 82%

“…It has been reported that CYP3A9, CYP3A18, and CYP3A62 are mainly expressed instead of CYP3A1 and CYP3A2 in rat intestine (28,29). In this study, we could not isolate these CYP3A isoforms because we used polyclonal CYP3A2 antibody that might have cross-reactivity to other CYP3A isoforms.…”

Section: Immunoblot Analysismentioning

confidence: 96%

Effects of Continuous Ingestion of Herbal Teas on Intestinal CYP3A in the Rat

et al. 2007

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“…This has been further confirmed by RT-PCR analysis (Zhang et al, 1996). More recently, a new CYP3A form was isolated from rat enterocytes that shares 97% similarity with CYP3A9 (Gushchin et al, 1999). The ready inducibility of P450s by drugs can lead to drug-drug interactions.…”

Section: Rat and Mouse Small Intestinal P450 Expressionmentioning

confidence: 77%

The Small Intestine as a Xenobiotic-Metabolizing Organ

Kaminsky

Zhang²

2003

Drug Metab Dispos

203

149

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“…Is CYP3A1 or CYP3A2 really present in the small intestine of normal Wistar rats? The presence of the CYP3A subfamily in rat small intestine has been reported (Watkins et al, 1987;de Waziers et al, 1990;Chiba et al, 1997), although some authors were unable to detect message for CYP3A1 or CYP3A2 (Zhang et al, 1996;Gushchin et al, 1999). Also, it was reported that a protein in enterocytes of male Wistar rats reacted with a commercially available antibody to CYP3A2, but RT-PCR analysis resulted in the amplification of a product, which corresponded to CYP3A1 and not to…”

Section: Discussionmentioning

confidence: 95%

EXPRESSION PROFILES OF DRUG-METABOLIZING ENZYME CYP3A AND DRUG EFFLUX TRANSPORTER MULTIDRUG RESISTANCE 1 SUBFAMILY mRNAS IN RAT SMALL INTESTINE

Takara

Ohnishi²,

Horibe³

et al. 2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:The purpose of this study is to examine the expression profiles of CYP3A1, CYP3A2, CYP3A9, and CYP3A18 mRNAs as well as multidrug resistance (mdr)1a and mdr1b mRNAs in the liver and small intestine of normal male Wistar rats using a reverse transcriptionpolymerase chain reaction (PCR). In the rat liver, the PCR products for CYP3A1, CYP3A2, and CYP3A18 were readily detectable, whereas CYP3A9 was slightly and mdr1a and mdr1b barely detected. Surprisingly, no PCR products for CYP3A1 and CYP3A2 were detected in the small intestine, but those for CYP3A9, CYP3A18, and mdr1a were readily detectable, and a faint band for mdr1b was also observed. Both CYP3A9 and CYP3A18 levels were found to be high in the duodenum and decreased from the top to bottom of the gut, indicating regional differences in both CYP3A9 and CYP3A18 expression in the small intestine. In contrast, mdr1a expression increased gradually from the upper to lower intestine. Consequently, it was suggested that drug metabolism in the small intestine of normal rats was mediated by CYP3A9 and CYP3A18 rather than CYP3A1 and CYP3A2. Also, regional differences of CYP3A9, CYP3A18, and mdr1a expression were found in the small intestine. The distributions of CYP3A9 and CYP3A18 were different from the distribution of mdr1a, suggesting the cooperative action of drug clearance pathways. This information is important to drug metabolism research based on ex vivo and in vivo studies using rats.

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A Novel Cytochrome P450 3A Isoenzyme in Rat Intestinal Microsomes

Cited by 21 publications

References 16 publications

Effects of Continuous Ingestion of Herbal Teas on Intestinal CYP3A in the Rat

Effects of Continuous Ingestion of Herbal Teas on Intestinal CYP3A in the Rat

The Small Intestine as a Xenobiotic-Metabolizing Organ

EXPRESSION PROFILES OF DRUG-METABOLIZING ENZYME CYP3A AND DRUG EFFLUX TRANSPORTER MULTIDRUG RESISTANCE 1 SUBFAMILY mRNAS IN RAT SMALL INTESTINE

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