The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina
•5-MCA-NAT, luzindole and NMH increase dopamine accumulation in developing retinas.•Luzindole inhibits dopamine levels stimulated by 5-MCA-NAT in developing retinas.•Benzo[e]pyrene reduces dopamine levels in both control and NMH-stimulated retinas.•Retinal dopamine levels are modulated by NRH:quinon...
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| Veröffentlicht in: | International journal of developmental neuroscience 2014-11, Vol.38 (1), p.119-126 |
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| creator | Sampaio, Lucia de Fatima Sobral Mesquita, Felipe Pantoja de Sousa, Paulo Robson Monteiro Silva, Jerônimo Lameira Alves, Claudio Nahum |
| description | •5-MCA-NAT, luzindole and NMH increase dopamine accumulation in developing retinas.•Luzindole inhibits dopamine levels stimulated by 5-MCA-NAT in developing retinas.•Benzo[e]pyrene reduces dopamine levels in both control and NMH-stimulated retinas.•Retinal dopamine levels are modulated by NRH:quinone reductase ligands in the retina.
NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−logEC50=11.62±0.34M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−logEC50=6.74±0.26M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−logIC50=7.4±0.28M) and NMH-stimulated (at 100nM and 1μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development. |
| doi_str_mv | 10.1016/j.ijdevneu.2014.09.001 |
| format | Article |
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NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−logEC50=11.62±0.34M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−logEC50=6.74±0.26M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−logIC50=7.4±0.28M) and NMH-stimulated (at 100nM and 1μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development.</description><identifier>ISSN: 0736-5748</identifier><identifier>EISSN: 1873-474X</identifier><identifier>DOI: 10.1016/j.ijdevneu.2014.09.001</identifier><identifier>PMID: 25218627</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>5-MCA-NAT ; Age Factors ; Animals ; Animals, Newborn ; Benzo[e]pyrene ; Chick Embryo ; Chickens ; Dopamine ; Dopamine - metabolism ; Dose-Response Relationship, Drug ; Drug Interactions ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation, Developmental - drug effects ; Melatonin receptors ; Models, Molecular ; Molecular Docking Simulation ; NAD(P)H Dehydrogenase (Quinone) - metabolism ; NRH:quinone reductase ; Protein Binding - drug effects ; Receptor, Melatonin, MT2 - antagonists & inhibitors ; Retina ; Retina - drug effects ; Retina - embryology ; Retina - enzymology ; Retina - growth & development ; Tetrahydronaphthalenes - pharmacology ; Tryptamines - pharmacology</subject><ispartof>International journal of developmental neuroscience, 2014-11, Vol.38 (1), p.119-126</ispartof><rights>2014 ISDN</rights><rights>Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5151-262e7b919893bb92d3285c6afbd902114f03586c28dfac53d18c22ba6ec22e1d3</citedby><cites>FETCH-LOGICAL-c5151-262e7b919893bb92d3285c6afbd902114f03586c28dfac53d18c22ba6ec22e1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.ijdevneu.2014.09.001$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2Fj.ijdevneu.2014.09.001$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25218627$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sampaio, Lucia de Fatima Sobral</creatorcontrib><creatorcontrib>Mesquita, Felipe Pantoja</creatorcontrib><creatorcontrib>de Sousa, Paulo Robson Monteiro</creatorcontrib><creatorcontrib>Silva, Jerônimo Lameira</creatorcontrib><creatorcontrib>Alves, Claudio Nahum</creatorcontrib><title>The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina</title><title>International journal of developmental neuroscience</title><addtitle>Int J Dev Neurosci</addtitle><description>•5-MCA-NAT, luzindole and NMH increase dopamine accumulation in developing retinas.•Luzindole inhibits dopamine levels stimulated by 5-MCA-NAT in developing retinas.•Benzo[e]pyrene reduces dopamine levels in both control and NMH-stimulated retinas.•Retinal dopamine levels are modulated by NRH:quinone reductase ligands in the retina.
NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−logEC50=11.62±0.34M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−logEC50=6.74±0.26M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−logIC50=7.4±0.28M) and NMH-stimulated (at 100nM and 1μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development.</description><subject>5-MCA-NAT</subject><subject>Age Factors</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Benzo[e]pyrene</subject><subject>Chick Embryo</subject><subject>Chickens</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Melatonin receptors</subject><subject>Models, Molecular</subject><subject>Molecular Docking Simulation</subject><subject>NAD(P)H Dehydrogenase (Quinone) - metabolism</subject><subject>NRH:quinone reductase</subject><subject>Protein Binding - drug effects</subject><subject>Receptor, Melatonin, MT2 - antagonists & inhibitors</subject><subject>Retina</subject><subject>Retina - drug effects</subject><subject>Retina - embryology</subject><subject>Retina - enzymology</subject><subject>Retina - growth & development</subject><subject>Tetrahydronaphthalenes - pharmacology</subject><subject>Tryptamines - pharmacology</subject><issn>0736-5748</issn><issn>1873-474X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV1v0zAUhiMEYt3gL0y-5CaZ7XzZXFF1HWs1ioQ6xJ3l2CedS2J3cVJUfgK_GkfZuGVXR7Kf9z22nii6JDghmBRX-8TsNRwtDAnFJEswTzAmr6IZYWUaZ2X243U0w2VaxHmZsbPo3Ps9xjjPcfY2OqM5Jayg5Sz6s30A1EIje2eNRdLKxu1QHn9ZzOPNfIuMVR1IDx6B1W4H1g0eaXeQrbGAGjhC41F1QpWx2tgd2ny7_fg4GOvCbQd6UH0Ih-zvUwuhDPVhnR5T7jDi6sGonwHsjZXvoje1bDy8f5oX0f3Ncru4je--fl4t5nexyklOYlpQKCtOOONpVXGqU8pyVci60hxTQrIapzkrFGW6lipPNWGK0koWEAYQnV5EH6beQ-ceB_C9aI1X0DTSQvidIEWZprxgnL0ATXnGWYZxQIsJVZ3zvoNaHDrTyu4kCBajMrEXz8rEqExgLoKyELx82jFULeh_sWdHAVhNwC_TwOmFtWJ9vVmv1tfL75vl_XiO-bTs09QVtMHRQCe8MmAVaNOB6oV25n_v_QszbcLG</recordid><startdate>201411</startdate><enddate>201411</enddate><creator>Sampaio, Lucia de Fatima Sobral</creator><creator>Mesquita, Felipe Pantoja</creator><creator>de Sousa, Paulo Robson Monteiro</creator><creator>Silva, Jerônimo Lameira</creator><creator>Alves, Claudio Nahum</creator><general>Elsevier Ltd</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>201411</creationdate><title>The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina</title><author>Sampaio, Lucia de Fatima Sobral ; Mesquita, Felipe Pantoja ; de Sousa, Paulo Robson Monteiro ; Silva, Jerônimo Lameira ; Alves, Claudio Nahum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5151-262e7b919893bb92d3285c6afbd902114f03586c28dfac53d18c22ba6ec22e1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>5-MCA-NAT</topic><topic>Age Factors</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Benzo[e]pyrene</topic><topic>Chick Embryo</topic><topic>Chickens</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Melatonin receptors</topic><topic>Models, Molecular</topic><topic>Molecular Docking Simulation</topic><topic>NAD(P)H Dehydrogenase (Quinone) - metabolism</topic><topic>NRH:quinone reductase</topic><topic>Protein Binding - drug effects</topic><topic>Receptor, Melatonin, MT2 - antagonists & inhibitors</topic><topic>Retina</topic><topic>Retina - drug effects</topic><topic>Retina - embryology</topic><topic>Retina - enzymology</topic><topic>Retina - growth & development</topic><topic>Tetrahydronaphthalenes - pharmacology</topic><topic>Tryptamines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sampaio, Lucia de Fatima Sobral</creatorcontrib><creatorcontrib>Mesquita, Felipe Pantoja</creatorcontrib><creatorcontrib>de Sousa, Paulo Robson Monteiro</creatorcontrib><creatorcontrib>Silva, Jerônimo Lameira</creatorcontrib><creatorcontrib>Alves, Claudio Nahum</creatorcontrib><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><collection>Neurosciences Abstracts</collection><jtitle>International journal of developmental neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sampaio, Lucia de Fatima Sobral</au><au>Mesquita, Felipe Pantoja</au><au>de Sousa, Paulo Robson Monteiro</au><au>Silva, Jerônimo Lameira</au><au>Alves, Claudio Nahum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina</atitle><jtitle>International journal of developmental neuroscience</jtitle><addtitle>Int J Dev Neurosci</addtitle><date>2014-11</date><risdate>2014</risdate><volume>38</volume><issue>1</issue><spage>119</spage><epage>126</epage><pages>119-126</pages><issn>0736-5748</issn><eissn>1873-474X</eissn><abstract>•5-MCA-NAT, luzindole and NMH increase dopamine accumulation in developing retinas.•Luzindole inhibits dopamine levels stimulated by 5-MCA-NAT in developing retinas.•Benzo[e]pyrene reduces dopamine levels in both control and NMH-stimulated retinas.•Retinal dopamine levels are modulated by NRH:quinone reductase ligands in the retina.
NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−logEC50=11.62±0.34M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−logEC50=6.74±0.26M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−logIC50=7.4±0.28M) and NMH-stimulated (at 100nM and 1μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>25218627</pmid><doi>10.1016/j.ijdevneu.2014.09.001</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 5-MCA-NAT Age Factors Animals Animals, Newborn Benzo[e]pyrene Chick Embryo Chickens Dopamine Dopamine - metabolism Dose-Response Relationship, Drug Drug Interactions Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Developmental - drug effects Melatonin receptors Models, Molecular Molecular Docking Simulation NAD(P)H Dehydrogenase (Quinone) - metabolism NRH:quinone reductase Protein Binding - drug effects Receptor, Melatonin, MT2 - antagonists & inhibitors Retina Retina - drug effects Retina - embryology Retina - enzymology Retina - growth & development Tetrahydronaphthalenes - pharmacology Tryptamines - pharmacology |
| title | The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina |
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