Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier
To investigate the influence of astrocytes on P-glycoprotein (Pgp) expression and intracellular accumulation of Pgp substrates, separate from their net transcellular transport across the blood-brain barrier (BBB). An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC)...
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| Veröffentlicht in: | Pharmaceutical research 2000-10, Vol.17 (10), p.1198-1205 |
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| creator | GAILLARD, Pieter Jaap VAN DER SANDT, Inez Cornelia VOORWINDEN, Levina Helena VU, Dung NIELSEN, Jette Lyngholm DE BOER, Albertus Gerrit BREIMER, Douwe Durk |
| description | To investigate the influence of astrocytes on P-glycoprotein (Pgp) expression and intracellular accumulation of Pgp substrates, separate from their net transcellular transport across the blood-brain barrier (BBB).
An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) monolayers or BCEC co-cultured with astrocytes.
BCEC+astrocyte co-cultures seemed to express a higher level of Pgp compared to BCEC monolayers. Inhibition of Pgp results in an increased intracellular accumulation of Pgp substrates in both BCEC monolayers and BCEC+astrocyte co-cultures, and increased the sensitivity for vinblastine mediated disruption of the in vitro BBB (called the vinblastine exclusion assay). BCEC monolayers were more sensitive to vinblastine mediated disruption compared to BCEC+astrocyte co-cultures. In the latter, but not in BCEC monolayers, an inhibitable polar transport of Pgp substrates was only found from the brain to the blood side of the filter.
Astrocytes increase the functional expression of Pgp in our in vitro BBB model. These results also illustrate that an important role for Pgp on the BBB is to protect the barrier against intracellular accumulation of cytotoxic BBB disrupting compounds. |
| doi_str_mv | 10.1023/A:1026406528530 |
| format | Article |
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An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) monolayers or BCEC co-cultured with astrocytes.
BCEC+astrocyte co-cultures seemed to express a higher level of Pgp compared to BCEC monolayers. Inhibition of Pgp results in an increased intracellular accumulation of Pgp substrates in both BCEC monolayers and BCEC+astrocyte co-cultures, and increased the sensitivity for vinblastine mediated disruption of the in vitro BBB (called the vinblastine exclusion assay). BCEC monolayers were more sensitive to vinblastine mediated disruption compared to BCEC+astrocyte co-cultures. In the latter, but not in BCEC monolayers, an inhibitable polar transport of Pgp substrates was only found from the brain to the blood side of the filter.
Astrocytes increase the functional expression of Pgp in our in vitro BBB model. These results also illustrate that an important role for Pgp on the BBB is to protect the barrier against intracellular accumulation of cytotoxic BBB disrupting compounds.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1026406528530</identifier><identifier>PMID: 11145224</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents, Phytogenic - pharmacokinetics ; Astrocytes - cytology ; Astrocytes - physiology ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology ; Biological and medical sciences ; Blood-Brain Barrier - physiology ; Brain - blood supply ; Caco-2 Cells - metabolism ; Capillaries - cytology ; Capillaries - metabolism ; Cattle ; Cell physiology ; Coculture Techniques ; Endothelium, Vascular - cytology ; Endothelium, Vascular - metabolism ; Fluorescent Dyes - pharmacokinetics ; Fundamental and applied biological sciences. Psychology ; General aspects ; Humans ; Medical sciences ; Membrane and intracellular transports ; Molecular and cellular biology ; Pharmacology. Drug treatments ; Rhodamine 123 - pharmacokinetics ; Transfection ; Vinblastine - pharmacokinetics</subject><ispartof>Pharmaceutical research, 2000-10, Vol.17 (10), p.1198-1205</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Oct 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-452fe65c8896b6b6128b8b6f284cb4145f1deb4c9c7ef17f51f0d5d4c34795013</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=832488$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11145224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GAILLARD, Pieter Jaap</creatorcontrib><creatorcontrib>VAN DER SANDT, Inez Cornelia</creatorcontrib><creatorcontrib>VOORWINDEN, Levina Helena</creatorcontrib><creatorcontrib>VU, Dung</creatorcontrib><creatorcontrib>NIELSEN, Jette Lyngholm</creatorcontrib><creatorcontrib>DE BOER, Albertus Gerrit</creatorcontrib><creatorcontrib>BREIMER, Douwe Durk</creatorcontrib><title>Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>To investigate the influence of astrocytes on P-glycoprotein (Pgp) expression and intracellular accumulation of Pgp substrates, separate from their net transcellular transport across the blood-brain barrier (BBB).
An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) monolayers or BCEC co-cultured with astrocytes.
BCEC+astrocyte co-cultures seemed to express a higher level of Pgp compared to BCEC monolayers. Inhibition of Pgp results in an increased intracellular accumulation of Pgp substrates in both BCEC monolayers and BCEC+astrocyte co-cultures, and increased the sensitivity for vinblastine mediated disruption of the in vitro BBB (called the vinblastine exclusion assay). BCEC monolayers were more sensitive to vinblastine mediated disruption compared to BCEC+astrocyte co-cultures. In the latter, but not in BCEC monolayers, an inhibitable polar transport of Pgp substrates was only found from the brain to the blood side of the filter.
Astrocytes increase the functional expression of Pgp in our in vitro BBB model. These results also illustrate that an important role for Pgp on the BBB is to protect the barrier against intracellular accumulation of cytotoxic BBB disrupting compounds.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - physiology</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier - physiology</subject><subject>Brain - blood supply</subject><subject>Caco-2 Cells - metabolism</subject><subject>Capillaries - cytology</subject><subject>Capillaries - metabolism</subject><subject>Cattle</subject><subject>Cell physiology</subject><subject>Coculture Techniques</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fluorescent Dyes - pharmacokinetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Membrane and intracellular transports</subject><subject>Molecular and cellular biology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rhodamine 123 - pharmacokinetics</subject><subject>Transfection</subject><subject>Vinblastine - pharmacokinetics</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkE1LxDAQhoMo7rp69iZFwVs1SSdt6m1Z_IIFPSh4K0k60S7dZk1acf-9WV09yMAMwzzz8s4QcszoBaM8u5xexZIDzQWXIqM7ZMxEkaUlhZddMqYFh1QWwEbkIIQFpVSyEvbJiDEGgnMYEzcNvXdm3WNIms54VAGT_g0TO3Smb1yn2gQ_Vx5DiE3ibPKYvrZr41be9dh0cSlR3_mjiULJ0tXYbrCNhm6dq1PtVRxr5X2D_pDsWdUGPNrWCXm-uX6a3aXzh9v72XSemkxAn0Z3FnNhpCxzHYNxqaXOLZdgNETzltWowZSmQMsKK5iltajBZFCUgrJsQs5_dKPP9wFDXy2bYLBtVYduCFXBBaNFDhE8_Qcu3ODj2aHinOc5gOQROtlCg15iXa18s1R-Xf3-MQJnW0AFo1rrVWea8MfJjIOU2RfLnoF9</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>GAILLARD, Pieter Jaap</creator><creator>VAN DER SANDT, Inez Cornelia</creator><creator>VOORWINDEN, Levina Helena</creator><creator>VU, Dung</creator><creator>NIELSEN, Jette Lyngholm</creator><creator>DE BOER, Albertus Gerrit</creator><creator>BREIMER, Douwe Durk</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20001001</creationdate><title>Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier</title><author>GAILLARD, Pieter Jaap ; VAN DER SANDT, Inez Cornelia ; VOORWINDEN, Levina Helena ; VU, Dung ; NIELSEN, Jette Lyngholm ; DE BOER, Albertus Gerrit ; BREIMER, Douwe Durk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-452fe65c8896b6b6128b8b6f284cb4145f1deb4c9c7ef17f51f0d5d4c34795013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents, Phytogenic - pharmacokinetics</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - physiology</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - physiology</topic><topic>Brain - blood supply</topic><topic>Caco-2 Cells - metabolism</topic><topic>Capillaries - cytology</topic><topic>Capillaries - metabolism</topic><topic>Cattle</topic><topic>Cell physiology</topic><topic>Coculture Techniques</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fluorescent Dyes - pharmacokinetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Membrane and intracellular transports</topic><topic>Molecular and cellular biology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rhodamine 123 - pharmacokinetics</topic><topic>Transfection</topic><topic>Vinblastine - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GAILLARD, Pieter Jaap</creatorcontrib><creatorcontrib>VAN DER SANDT, Inez Cornelia</creatorcontrib><creatorcontrib>VOORWINDEN, Levina Helena</creatorcontrib><creatorcontrib>VU, Dung</creatorcontrib><creatorcontrib>NIELSEN, Jette Lyngholm</creatorcontrib><creatorcontrib>DE BOER, Albertus Gerrit</creatorcontrib><creatorcontrib>BREIMER, Douwe Durk</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GAILLARD, Pieter Jaap</au><au>VAN DER SANDT, Inez Cornelia</au><au>VOORWINDEN, Levina Helena</au><au>VU, Dung</au><au>NIELSEN, Jette Lyngholm</au><au>DE BOER, Albertus Gerrit</au><au>BREIMER, Douwe Durk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>17</volume><issue>10</issue><spage>1198</spage><epage>1205</epage><pages>1198-1205</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>To investigate the influence of astrocytes on P-glycoprotein (Pgp) expression and intracellular accumulation of Pgp substrates, separate from their net transcellular transport across the blood-brain barrier (BBB).
An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) monolayers or BCEC co-cultured with astrocytes.
BCEC+astrocyte co-cultures seemed to express a higher level of Pgp compared to BCEC monolayers. Inhibition of Pgp results in an increased intracellular accumulation of Pgp substrates in both BCEC monolayers and BCEC+astrocyte co-cultures, and increased the sensitivity for vinblastine mediated disruption of the in vitro BBB (called the vinblastine exclusion assay). BCEC monolayers were more sensitive to vinblastine mediated disruption compared to BCEC+astrocyte co-cultures. In the latter, but not in BCEC monolayers, an inhibitable polar transport of Pgp substrates was only found from the brain to the blood side of the filter.
Astrocytes increase the functional expression of Pgp in our in vitro BBB model. These results also illustrate that an important role for Pgp on the BBB is to protect the barrier against intracellular accumulation of cytotoxic BBB disrupting compounds.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11145224</pmid><doi>10.1023/A:1026406528530</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Antineoplastic agents Antineoplastic Agents, Phytogenic - pharmacokinetics Astrocytes - cytology Astrocytes - physiology ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology Biological and medical sciences Blood-Brain Barrier - physiology Brain - blood supply Caco-2 Cells - metabolism Capillaries - cytology Capillaries - metabolism Cattle Cell physiology Coculture Techniques Endothelium, Vascular - cytology Endothelium, Vascular - metabolism Fluorescent Dyes - pharmacokinetics Fundamental and applied biological sciences. Psychology General aspects Humans Medical sciences Membrane and intracellular transports Molecular and cellular biology Pharmacology. Drug treatments Rhodamine 123 - pharmacokinetics Transfection Vinblastine - pharmacokinetics |
| title | Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier |
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