Human embryonic cytochrome p450s: Phenoxazone ethers as probes for expression of functional isoforms during organogenesis
Human embryonic tissues were investigated during the period of organogenesis with a combination of substrate probes, selective inhibitors and immunoprobes in terms of their capacity to express functional P450 isoforms. A series of phenoxazone ethers utilized as substrate probes revealed that human e...
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Veröffentlicht in: | Biochemical pharmacology 1991-11, Vol.42 (12), p.2377-2385 |
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description | Human embryonic tissues were investigated during the period of organogenesis with a combination of substrate probes, selective inhibitors and immunoprobes in terms of their capacity to express functional P450 isoforms. A series of phenoxazone ethers utilized as substrate probes revealed that human embryonic hepatic, pulmonary, renal, adrenal and cardiac tissues each contained a complement of functional P450 isoforms when analyzed between days 50 and 60 of gestation. Preparations of each of these tissues contained isoforms capable of catalyzing O-demethylation, O-deethylation, O-depentylation and O-debenzylation of the respective phenoxazone ethers. Investigations with chemical inhibitors and inhibitory antibodies as well as comparisons with vector-expressed, human P450 isoforms suggested that isoforms of P450 subfamilies 1A, 2B, 2C or 3A were not major contributors to any of the observed reactions. The P450-dependent reactions studied exhibited several unexpected and unusual characteristics including a preference for NADH over NADPH as the initial electron donor. Results were consistent with the concept that conceptal-specific P450 isoforms participate in the human embryonic O-dealkylation/debenzylation probe reactions investigated. |
doi_str_mv | 10.1016/0006-2952(91)90244-Y |
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A series of phenoxazone ethers utilized as substrate probes revealed that human embryonic hepatic, pulmonary, renal, adrenal and cardiac tissues each contained a complement of functional P450 isoforms when analyzed between days 50 and 60 of gestation. Preparations of each of these tissues contained isoforms capable of catalyzing O-demethylation, O-deethylation, O-depentylation and O-debenzylation of the respective phenoxazone ethers. Investigations with chemical inhibitors and inhibitory antibodies as well as comparisons with vector-expressed, human P450 isoforms suggested that isoforms of P450 subfamilies 1A, 2B, 2C or 3A were not major contributors to any of the observed reactions. The P450-dependent reactions studied exhibited several unexpected and unusual characteristics including a preference for NADH over NADPH as the initial electron donor. Results were consistent with the concept that conceptal-specific P450 isoforms participate in the human embryonic O-dealkylation/debenzylation probe reactions investigated.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(91)90244-Y</identifier><identifier>PMID: 1764121</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Analytical, structural and metabolic biochemistry ; Antibodies, Monoclonal ; Benzoflavones - pharmacology ; Biological and medical sciences ; Biotransformation ; Carbon Monoxide - pharmacology ; Cytochrome P-450 CYP2B1 ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System - immunology ; Cytochrome P-450 Enzyme System - metabolism ; Embryo, Mammalian - drug effects ; Embryo, Mammalian - enzymology ; Enzymes and enzyme inhibitors ; Ethers - pharmacology ; Fundamental and applied biological sciences. Psychology ; Humans ; Isoenzymes - immunology ; Isoenzymes - metabolism ; Metyrapone - pharmacology ; Morphogenesis - drug effects ; Orphenadrine - pharmacology ; Oxazines - pharmacology ; Oxidoreductases ; Oxidoreductases - antagonists & inhibitors ; Xenobiotics - pharmacology</subject><ispartof>Biochemical pharmacology, 1991-11, Vol.42 (12), p.2377-2385</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-de3e78f4762784062564beb0ecfdb6f0c186e593c4c59d49d57876eacf2089d03</citedby><cites>FETCH-LOGICAL-c386t-de3e78f4762784062564beb0ecfdb6f0c186e593c4c59d49d57876eacf2089d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/000629529190244Y$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5091345$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1764121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Qwihee P.</creatorcontrib><creatorcontrib>Fantel, Alan G.</creatorcontrib><creatorcontrib>Juchau, Mont R.</creatorcontrib><title>Human embryonic cytochrome p450s: Phenoxazone ethers as probes for expression of functional isoforms during organogenesis</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>Human embryonic tissues were investigated during the period of organogenesis with a combination of substrate probes, selective inhibitors and immunoprobes in terms of their capacity to express functional P450 isoforms. A series of phenoxazone ethers utilized as substrate probes revealed that human embryonic hepatic, pulmonary, renal, adrenal and cardiac tissues each contained a complement of functional P450 isoforms when analyzed between days 50 and 60 of gestation. Preparations of each of these tissues contained isoforms capable of catalyzing O-demethylation, O-deethylation, O-depentylation and O-debenzylation of the respective phenoxazone ethers. Investigations with chemical inhibitors and inhibitory antibodies as well as comparisons with vector-expressed, human P450 isoforms suggested that isoforms of P450 subfamilies 1A, 2B, 2C or 3A were not major contributors to any of the observed reactions. The P450-dependent reactions studied exhibited several unexpected and unusual characteristics including a preference for NADH over NADPH as the initial electron donor. Results were consistent with the concept that conceptal-specific P450 isoforms participate in the human embryonic O-dealkylation/debenzylation probe reactions investigated.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antibodies, Monoclonal</subject><subject>Benzoflavones - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Carbon Monoxide - pharmacology</subject><subject>Cytochrome P-450 CYP2B1</subject><subject>Cytochrome P-450 Enzyme Inhibitors</subject><subject>Cytochrome P-450 Enzyme System - immunology</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Embryo, Mammalian - drug effects</subject><subject>Embryo, Mammalian - enzymology</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Ethers - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Isoenzymes - immunology</subject><subject>Isoenzymes - metabolism</subject><subject>Metyrapone - pharmacology</subject><subject>Morphogenesis - drug effects</subject><subject>Orphenadrine - pharmacology</subject><subject>Oxazines - pharmacology</subject><subject>Oxidoreductases</subject><subject>Oxidoreductases - antagonists & inhibitors</subject><subject>Xenobiotics - pharmacology</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi1EVbaFfwCSD6iCQ8BOHH9wQKqqQpEqwQEOPVmOM941SuzFk6Auv54su2pvnMbj95nR6CHkJWfvOOPyPWNMVrVp6zeGvzWsFqK6e0JWXKtm-Zb6KVk9IM_IGeLPfaslPyWnXEnBa74iu5t5dInC2JVdTtFTv5uy35Q8At2KluEH-m0DKd-7PzkBhWkDBalDui25A6QhFwr32wKIMSeaAw1z8tPydgONmJd8RNrPJaY1zWXtUl5DAoz4nJwENyC8ONZz8uPT9ferm-r26-cvV5e3lW-0nKoeGlA6CCVrpQWTdStFBx0DH_pOBua5ltCaxgvfml6YvlVaSXA-1EybnjXn5OKwd7n41ww42TGih2FwCfKMVtWt1kqZBRQH0JeMWCDYbYmjKzvLmd0bt3t_dq_TGm7_Gbd3y9ir4_65G6F_HDooXvLXx9yhd0MoLvmID1jLDG9Eu2AfDxgsLn5HKBZ9hOShjwX8ZPsc_3_HXyF-n0I</recordid><startdate>19911127</startdate><enddate>19911127</enddate><creator>Lee, Qwihee P.</creator><creator>Fantel, Alan G.</creator><creator>Juchau, Mont R.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>19911127</creationdate><title>Human embryonic cytochrome p450s: Phenoxazone ethers as probes for expression of functional isoforms during organogenesis</title><author>Lee, Qwihee P. ; Fantel, Alan G. ; Juchau, Mont R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-de3e78f4762784062564beb0ecfdb6f0c186e593c4c59d49d57876eacf2089d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Antibodies, Monoclonal</topic><topic>Benzoflavones - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Carbon Monoxide - pharmacology</topic><topic>Cytochrome P-450 CYP2B1</topic><topic>Cytochrome P-450 Enzyme Inhibitors</topic><topic>Cytochrome P-450 Enzyme System - immunology</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Embryo, Mammalian - drug effects</topic><topic>Embryo, Mammalian - enzymology</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Ethers - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Isoenzymes - immunology</topic><topic>Isoenzymes - metabolism</topic><topic>Metyrapone - pharmacology</topic><topic>Morphogenesis - drug effects</topic><topic>Orphenadrine - pharmacology</topic><topic>Oxazines - pharmacology</topic><topic>Oxidoreductases</topic><topic>Oxidoreductases - antagonists & inhibitors</topic><topic>Xenobiotics - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Qwihee P.</creatorcontrib><creatorcontrib>Fantel, Alan G.</creatorcontrib><creatorcontrib>Juchau, Mont R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Qwihee P.</au><au>Fantel, Alan G.</au><au>Juchau, Mont R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human embryonic cytochrome p450s: Phenoxazone ethers as probes for expression of functional isoforms during organogenesis</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1991-11-27</date><risdate>1991</risdate><volume>42</volume><issue>12</issue><spage>2377</spage><epage>2385</epage><pages>2377-2385</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>Human embryonic tissues were investigated during the period of organogenesis with a combination of substrate probes, selective inhibitors and immunoprobes in terms of their capacity to express functional P450 isoforms. A series of phenoxazone ethers utilized as substrate probes revealed that human embryonic hepatic, pulmonary, renal, adrenal and cardiac tissues each contained a complement of functional P450 isoforms when analyzed between days 50 and 60 of gestation. Preparations of each of these tissues contained isoforms capable of catalyzing O-demethylation, O-deethylation, O-depentylation and O-debenzylation of the respective phenoxazone ethers. Investigations with chemical inhibitors and inhibitory antibodies as well as comparisons with vector-expressed, human P450 isoforms suggested that isoforms of P450 subfamilies 1A, 2B, 2C or 3A were not major contributors to any of the observed reactions. The P450-dependent reactions studied exhibited several unexpected and unusual characteristics including a preference for NADH over NADPH as the initial electron donor. Results were consistent with the concept that conceptal-specific P450 isoforms participate in the human embryonic O-dealkylation/debenzylation probe reactions investigated.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>1764121</pmid><doi>10.1016/0006-2952(91)90244-Y</doi><tpages>9</tpages></addata></record> |
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subjects | Analytical, structural and metabolic biochemistry Antibodies, Monoclonal Benzoflavones - pharmacology Biological and medical sciences Biotransformation Carbon Monoxide - pharmacology Cytochrome P-450 CYP2B1 Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System - immunology Cytochrome P-450 Enzyme System - metabolism Embryo, Mammalian - drug effects Embryo, Mammalian - enzymology Enzymes and enzyme inhibitors Ethers - pharmacology Fundamental and applied biological sciences. Psychology Humans Isoenzymes - immunology Isoenzymes - metabolism Metyrapone - pharmacology Morphogenesis - drug effects Orphenadrine - pharmacology Oxazines - pharmacology Oxidoreductases Oxidoreductases - antagonists & inhibitors Xenobiotics - pharmacology |
title | Human embryonic cytochrome p450s: Phenoxazone ethers as probes for expression of functional isoforms during organogenesis |
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