Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain
Transport of 3H‐labelled thyrotropin‐releasing hormone (TRH) across the blood‐brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10‐−3 to 1.22 × 10‐−...
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| Veröffentlicht in: | Journal of neurochemistry 1988-07, Vol.51 (1), p.252-257 |
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| creator | Zloković, Berislav V. Lipovac, Milo N. Begley, David J. Davson, Hugh Rakić, Ljubiša |
| description | Transport of 3H‐labelled thyrotropin‐releasing hormone (TRH) across the blood‐brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10‐−3 to 1.22 × 10‐−3 ml min−1 g−1, in the parietal cortex, caudate nucleus, and hippocampus. Regional Kin values for [3H]TRH were significantly reduced by 43–48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood‐brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [3H]TRH regional Kin values similar to that obtained with 2 mM bacitracin alone was obtained. l‐Prolinamide, the N‐terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [3H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood‐brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood‐brain barrier, the rate of transfer being some three times higher than that of d‐mannitol. |
| doi_str_mv | 10.1111/j.1471-4159.1988.tb04864.x |
| format | Article |
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The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10‐−3 to 1.22 × 10‐−3 ml min−1 g−1, in the parietal cortex, caudate nucleus, and hippocampus. Regional Kin values for [3H]TRH were significantly reduced by 43–48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood‐brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [3H]TRH regional Kin values similar to that obtained with 2 mM bacitracin alone was obtained. l‐Prolinamide, the N‐terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [3H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood‐brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood‐brain barrier, the rate of transfer being some three times higher than that of d‐mannitol.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.1988.tb04864.x</identifier><identifier>PMID: 3132534</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Bacitracin - pharmacology ; Biological and medical sciences ; Blood-Brain Barrier ; Brain - blood supply ; Brain - drug effects ; Brain - metabolism ; Capillary Permeability ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Female ; Fundamental and applied biological sciences. Psychology ; Guinea pig ; Guinea Pigs ; Hippocampus - drug effects ; Hippocampus - metabolism ; Male ; Mannitol - metabolism ; Parietal Lobe - drug effects ; Parietal Lobe - metabolism ; Perfused brain ; Perfusion ; Proline - analogs & derivatives ; Proline - pharmacology ; thyroid-stimulating hormone-releasing hormone ; Thyrotropin-Releasing Hormone - metabolism ; Thyrotropin‐releasing hormone ; Unidirectional transfer constant ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of neurochemistry, 1988-07, Vol.51 (1), p.252-257</ispartof><rights>1989 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4102-a67216789a76c57f1add72a619eb3ac268513f6c6871ca1585ee2d7ddcf7a5bf3</citedby><cites>FETCH-LOGICAL-c4102-a67216789a76c57f1add72a619eb3ac268513f6c6871ca1585ee2d7ddcf7a5bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.1988.tb04864.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.1988.tb04864.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7071904$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3132534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zloković, Berislav V.</creatorcontrib><creatorcontrib>Lipovac, Milo N.</creatorcontrib><creatorcontrib>Begley, David J.</creatorcontrib><creatorcontrib>Davson, Hugh</creatorcontrib><creatorcontrib>Rakić, Ljubiša</creatorcontrib><title>Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Transport of 3H‐labelled thyrotropin‐releasing hormone (TRH) across the blood‐brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10‐−3 to 1.22 × 10‐−3 ml min−1 g−1, in the parietal cortex, caudate nucleus, and hippocampus. Regional Kin values for [3H]TRH were significantly reduced by 43–48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood‐brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [3H]TRH regional Kin values similar to that obtained with 2 mM bacitracin alone was obtained. l‐Prolinamide, the N‐terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [3H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood‐brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood‐brain barrier, the rate of transfer being some three times higher than that of d‐mannitol.</description><subject>Animals</subject><subject>Bacitracin - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier</subject><subject>Brain - blood supply</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Capillary Permeability</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea pig</subject><subject>Guinea Pigs</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Male</subject><subject>Mannitol - metabolism</subject><subject>Parietal Lobe - drug effects</subject><subject>Parietal Lobe - metabolism</subject><subject>Perfused brain</subject><subject>Perfusion</subject><subject>Proline - analogs & derivatives</subject><subject>Proline - pharmacology</subject><subject>thyroid-stimulating hormone-releasing hormone</subject><subject>Thyrotropin-Releasing Hormone - metabolism</subject><subject>Thyrotropin‐releasing hormone</subject><subject>Unidirectional transfer constant</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkcFu1DAURS0EKkPhE5AshNhN8HMS22GB1BlBW1RBRcvaeuM4rUcZe2onakdiwSfwjXwJSSeaLcIbL-55108-hLwBlsFw3q8zKCTMCyirDCqlsm7FCiWK7OEJmR2ip2TGGOfznBX8OXmR0poxEIWAI3KUQ87LvJiRn1dtuKeX1tsuYueCp6Gh17e7GLoYts7_-fX7u20tJudv6FmIm-AtPTExpES7W0sXbQj1AC0iOk8XGKOzcexAT889vXJdP7THpk-2pqe98xbppbuhj_xL8qzBNtlX031Mfnz-dL08m198Oz1fnlzMTQGMz1FIDkKqCqUwpWwA61pyFFDZVY6GC1VC3ggjlASDUKrSWl7LujaNxHLV5Mfk3b53G8Ndb1OnNy4Z27bobeiTloqXknP5TxCKSrFKjeCHPfj4E9E2ehvdBuNOA9OjI73Wowg9itCjIz050g_D8OvplX61sfVhdJIy5G-nHJPBtonojUsHTDIJFRuxj3vs3rV29x8L6C9fl7zk-V-TVLC1</recordid><startdate>198807</startdate><enddate>198807</enddate><creator>Zloković, Berislav V.</creator><creator>Lipovac, Milo N.</creator><creator>Begley, David J.</creator><creator>Davson, Hugh</creator><creator>Rakić, Ljubiša</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>198807</creationdate><title>Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain</title><author>Zloković, Berislav V. ; Lipovac, Milo N. ; Begley, David J. ; Davson, Hugh ; Rakić, Ljubiša</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4102-a67216789a76c57f1add72a619eb3ac268513f6c6871ca1585ee2d7ddcf7a5bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Animals</topic><topic>Bacitracin - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier</topic><topic>Brain - blood supply</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Capillary Permeability</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea pig</topic><topic>Guinea Pigs</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Male</topic><topic>Mannitol - metabolism</topic><topic>Parietal Lobe - drug effects</topic><topic>Parietal Lobe - metabolism</topic><topic>Perfused brain</topic><topic>Perfusion</topic><topic>Proline - analogs & derivatives</topic><topic>Proline - pharmacology</topic><topic>thyroid-stimulating hormone-releasing hormone</topic><topic>Thyrotropin-Releasing Hormone - metabolism</topic><topic>Thyrotropin‐releasing hormone</topic><topic>Unidirectional transfer constant</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zloković, Berislav V.</creatorcontrib><creatorcontrib>Lipovac, Milo N.</creatorcontrib><creatorcontrib>Begley, David J.</creatorcontrib><creatorcontrib>Davson, Hugh</creatorcontrib><creatorcontrib>Rakić, Ljubiša</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>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zloković, Berislav V.</au><au>Lipovac, Milo N.</au><au>Begley, David J.</au><au>Davson, Hugh</au><au>Rakić, Ljubiša</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1988-07</date><risdate>1988</risdate><volume>51</volume><issue>1</issue><spage>252</spage><epage>257</epage><pages>252-257</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Transport of 3H‐labelled thyrotropin‐releasing hormone (TRH) across the blood‐brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10‐−3 to 1.22 × 10‐−3 ml min−1 g−1, in the parietal cortex, caudate nucleus, and hippocampus. Regional Kin values for [3H]TRH were significantly reduced by 43–48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood‐brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [3H]TRH regional Kin values similar to that obtained with 2 mM bacitracin alone was obtained. l‐Prolinamide, the N‐terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [3H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood‐brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood‐brain barrier, the rate of transfer being some three times higher than that of d‐mannitol.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>3132534</pmid><doi>10.1111/j.1471-4159.1988.tb04864.x</doi><tpages>6</tpages></addata></record> |
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| ispartof | Journal of neurochemistry, 1988-07, Vol.51 (1), p.252-257 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Bacitracin - pharmacology Biological and medical sciences Blood-Brain Barrier Brain - blood supply Brain - drug effects Brain - metabolism Capillary Permeability Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Female Fundamental and applied biological sciences. Psychology Guinea pig Guinea Pigs Hippocampus - drug effects Hippocampus - metabolism Male Mannitol - metabolism Parietal Lobe - drug effects Parietal Lobe - metabolism Perfused brain Perfusion Proline - analogs & derivatives Proline - pharmacology thyroid-stimulating hormone-releasing hormone Thyrotropin-Releasing Hormone - metabolism Thyrotropin‐releasing hormone Unidirectional transfer constant Vertebrates: nervous system and sense organs |
| title | Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain |
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