Intestinal Expression and Metabolic Activity of the CYP3A Subfamily in Female Rats
The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female...
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Veröffentlicht in: | Biological & pharmaceutical bulletin 2005, Vol.28(2), pp.311-315 |
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creator | Aiba, Tetsuya Yoshinaga, Mariko Ishida, Kazuya Takehara, Yutaka Hashimoto, Yukiya |
description | The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6β-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes. |
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CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6β-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.28.311</identifier><identifier>PMID: 15684490</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Aryl Hydrocarbon Hydroxylases - biosynthesis ; Aryl Hydrocarbon Hydroxylases - genetics ; Aryl Hydrocarbon Hydroxylases - metabolism ; CYP3A9 ; Cytochrome P-450 CYP3A ; Female ; Gene Expression Regulation, Enzymologic - physiology ; intestinal metabolism ; Intestinal Mucosa - metabolism ; Intestines - enzymology ; Male ; Microsomes, Liver - enzymology ; Microsomes, Liver - metabolism ; Oxidoreductases, N-Demethylating - biosynthesis ; Oxidoreductases, N-Demethylating - genetics ; Oxidoreductases, N-Demethylating - metabolism ; Rats ; Rats, Wistar ; rifabutin ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Substrate Specificity ; testosterone</subject><ispartof>Biological and Pharmaceutical Bulletin, 2005, Vol.28(2), pp.311-315</ispartof><rights>2005 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c621t-3e373df777efde471bc9880f7b0d19413f0523361f0fa276992282869612bad13</citedby><cites>FETCH-LOGICAL-c621t-3e373df777efde471bc9880f7b0d19413f0523361f0fa276992282869612bad13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15684490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aiba, Tetsuya</creatorcontrib><creatorcontrib>Yoshinaga, Mariko</creatorcontrib><creatorcontrib>Ishida, Kazuya</creatorcontrib><creatorcontrib>Takehara, Yutaka</creatorcontrib><creatorcontrib>Hashimoto, Yukiya</creatorcontrib><title>Intestinal Expression and Metabolic Activity of the CYP3A Subfamily in Female Rats</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6β-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes.</description><subject>Animals</subject><subject>Aryl Hydrocarbon Hydroxylases - biosynthesis</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>CYP3A9</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Female</subject><subject>Gene Expression Regulation, Enzymologic - physiology</subject><subject>intestinal metabolism</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - enzymology</subject><subject>Male</subject><subject>Microsomes, Liver - enzymology</subject><subject>Microsomes, Liver - metabolism</subject><subject>Oxidoreductases, N-Demethylating - biosynthesis</subject><subject>Oxidoreductases, N-Demethylating - genetics</subject><subject>Oxidoreductases, N-Demethylating - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>rifabutin</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Substrate Specificity</subject><subject>testosterone</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE2LFDEQQIMo7rh68QdIQPAg9JhKuvNxkmHY1YUVZdWDp5DurrgZ-mM2SYvz780y4wpeKod6vFCPkJfA1sBr_a7dt2uu1wLgEVmBqFXVcGgekxUzoCsJjT4jz1LaMcYU4-IpOYNG6ro2bEVurqaMKYfJDfTi9z5iSmGeqJt6-gmza-chdHTT5fAr5AOdPc23SLc_vogN_bq03o1hONAw0Usc3YD0xuX0nDzxbkj44vSek--XF9-2H6vrzx-utpvrqpMcciVQKNF7pRT6HmsFbWe0Zl61rAdTg_Cs4UJI8Mw7rqQxnGuupZHAW9eDOCdvjt59nO-WcoQdQ-pwGNyE85KsVMJIxlUBX_8H7uYllouThVKh_KHNve7tkerinFJEb_cxjC4eLDB739mWzpZrWzoX-NVJubQj9v_QU9gCvD8Cu5TdT3wAXMyhG_Cvix9HUT5sulsXLU7iD4utjOc</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Aiba, Tetsuya</creator><creator>Yoshinaga, Mariko</creator><creator>Ishida, Kazuya</creator><creator>Takehara, Yutaka</creator><creator>Hashimoto, Yukiya</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050201</creationdate><title>Intestinal Expression and Metabolic Activity of the CYP3A Subfamily in Female Rats</title><author>Aiba, Tetsuya ; Yoshinaga, Mariko ; Ishida, Kazuya ; Takehara, Yutaka ; Hashimoto, Yukiya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c621t-3e373df777efde471bc9880f7b0d19413f0523361f0fa276992282869612bad13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Aryl Hydrocarbon Hydroxylases - biosynthesis</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>CYP3A9</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Female</topic><topic>Gene Expression Regulation, Enzymologic - physiology</topic><topic>intestinal metabolism</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestines - enzymology</topic><topic>Male</topic><topic>Microsomes, Liver - enzymology</topic><topic>Microsomes, Liver - metabolism</topic><topic>Oxidoreductases, N-Demethylating - biosynthesis</topic><topic>Oxidoreductases, N-Demethylating - genetics</topic><topic>Oxidoreductases, N-Demethylating - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>rifabutin</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Substrate Specificity</topic><topic>testosterone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aiba, Tetsuya</creatorcontrib><creatorcontrib>Yoshinaga, Mariko</creatorcontrib><creatorcontrib>Ishida, Kazuya</creatorcontrib><creatorcontrib>Takehara, Yutaka</creatorcontrib><creatorcontrib>Hashimoto, Yukiya</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aiba, Tetsuya</au><au>Yoshinaga, Mariko</au><au>Ishida, Kazuya</au><au>Takehara, Yutaka</au><au>Hashimoto, Yukiya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intestinal Expression and Metabolic Activity of the CYP3A Subfamily in Female Rats</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>28</volume><issue>2</issue><spage>311</spage><epage>315</epage><pages>311-315</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6β-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>15684490</pmid><doi>10.1248/bpb.28.311</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Aryl Hydrocarbon Hydroxylases - biosynthesis Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - metabolism CYP3A9 Cytochrome P-450 CYP3A Female Gene Expression Regulation, Enzymologic - physiology intestinal metabolism Intestinal Mucosa - metabolism Intestines - enzymology Male Microsomes, Liver - enzymology Microsomes, Liver - metabolism Oxidoreductases, N-Demethylating - biosynthesis Oxidoreductases, N-Demethylating - genetics Oxidoreductases, N-Demethylating - metabolism Rats Rats, Wistar rifabutin RNA, Messenger - biosynthesis RNA, Messenger - genetics Substrate Specificity testosterone |
title | Intestinal Expression and Metabolic Activity of the CYP3A Subfamily in Female Rats |
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