Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells
Cell membranes were prepared from the multidrug resistant, P-glycoprotein expressing human lymphoblastoid cell line CCRF-ADR 5000. The P-glycoprotein of these membranes possessed high affinity binding sites for [ 3H]vinblastine, with a K d of 8 ± 2 nM and B max of 17 ± 8 pmol/mg of protein. The bind...
Gespeichert in:
| Veröffentlicht in: | European journal of pharmacology 1994-12, Vol.288 (1), p.105-114 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 114 |
|---|---|
| container_issue | 1 |
| container_start_page | 105 |
| container_title | European journal of pharmacology |
| container_volume | 288 |
| creator | Malkhandi, Joy Ferry, David R. Boer, Rainer Gekeler, Volker Ise, Wolfgang Keer, David J. |
| description | Cell membranes were prepared from the multidrug resistant, P-glycoprotein expressing human lymphoblastoid cell line CCRF-ADR 5000. The P-glycoprotein of these membranes possessed high affinity binding sites for [
3H]vinblastine, with a
K
d of 8 ± 2 nM and
B
max of 17 ± 8 pmol/mg of protein. The binding of [
3H]vinblastine to P-glycoprotein was not ATP-dependent, and was inhibited by cytotoxic drugs with the following potency order; vincristine > doxorubicin > etoposide. The 1,4-dihydropyridine and multidrug resistance reversing agent, dexniguldipine-HCl, inhibited binding with a
K
i value of 37 nM. The multidrug resistance reversing agent cyclosporin A, and the cytotoxics doxorubicin and etoposide did not alter the kinetics of [
3H]vinblastine dissociation from P-glycoprotein; however, the 1,4-dihydropyridines dexniguldipine-HCl and nicardipine accelerated dissociation of [
3H]vinblastine. These data suggest that P-glycoprotein possesses at least two allosterically coupled drug acceptor sites; receptor site 1 which binds vinblastine, doxorubucin, etoposide and cyclosporin A, and receptor site 2 which binds dexniguldipine-HCl and other 1,4-dihydropyridines. |
| doi_str_mv | 10.1016/0922-4106(94)90015-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_77799589</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>0922410694900159</els_id><sourcerecordid>77799589</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-a2a57560efc48ce44882b72e1050cf6d886bcfb0ccdafba25eeba2699556e2ed3</originalsourceid><addsrcrecordid>eNp9kMGKFDEQhnNQ1nX1DRRyENFDa9KTpDsXYel1HWFBWfQkEtLp6rEkk4xJZtl9e9POMEcvKUh9f_HzEfKCs3eccfWe6bZtBGfqjRZvNWNcNvoROT99PyFPc_7NGNNcizNy1nVMCtWek_sruA-42fsJdxigWQ-eYqaW7mKBUKj1PuYCCR3F8AtHLDHRONMfdLX-eYdh9DaXGqQjhgnDhpZIvzYb_-DiLtUTGBZ6GG6v6eXVLZW1AnXgfX5GHs_WZ3h-nBfk-_XHb8O6ufny6fNwedO4Va9KY1srO6kYzE70DoTo-3bsWuBMMjerqe_V6OaROTfZebStBKiv0lpKBS1Mqwvy-nC31vmzh1zMFvPSwAaI-2y6rqtwrysoDqBLMecEs9kl3Nr0YDgzi2Sz2DSLTaOF-SfZLLGXx_v7cQvTKXQ0XPevjnubnfVzssFhPmErwTgXvGIfDhhUF3cIyWSHEBxMmMAVM0X8f4-_p6uaXA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>77799589</pqid></control><display><type>article</type><title>Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><source>Alma/SFX Local Collection</source><creator>Malkhandi, Joy ; Ferry, David R. ; Boer, Rainer ; Gekeler, Volker ; Ise, Wolfgang ; Keer, David J.</creator><creatorcontrib>Malkhandi, Joy ; Ferry, David R. ; Boer, Rainer ; Gekeler, Volker ; Ise, Wolfgang ; Keer, David J.</creatorcontrib><description>Cell membranes were prepared from the multidrug resistant, P-glycoprotein expressing human lymphoblastoid cell line CCRF-ADR 5000. The P-glycoprotein of these membranes possessed high affinity binding sites for [
3H]vinblastine, with a
K
d of 8 ± 2 nM and
B
max of 17 ± 8 pmol/mg of protein. The binding of [
3H]vinblastine to P-glycoprotein was not ATP-dependent, and was inhibited by cytotoxic drugs with the following potency order; vincristine > doxorubicin > etoposide. The 1,4-dihydropyridine and multidrug resistance reversing agent, dexniguldipine-HCl, inhibited binding with a
K
i value of 37 nM. The multidrug resistance reversing agent cyclosporin A, and the cytotoxics doxorubicin and etoposide did not alter the kinetics of [
3H]vinblastine dissociation from P-glycoprotein; however, the 1,4-dihydropyridines dexniguldipine-HCl and nicardipine accelerated dissociation of [
3H]vinblastine. These data suggest that P-glycoprotein possesses at least two allosterically coupled drug acceptor sites; receptor site 1 which binds vinblastine, doxorubucin, etoposide and cyclosporin A, and receptor site 2 which binds dexniguldipine-HCl and other 1,4-dihydropyridines.</description><identifier>ISSN: 0922-4106</identifier><identifier>ISSN: 0014-2999</identifier><identifier>DOI: 10.1016/0922-4106(94)90015-9</identifier><identifier>PMID: 7705462</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Allosteric interaction ; Allosteric Regulation ; Antineoplastic agents ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Binding, Competitive - drug effects ; Biological and medical sciences ; Calcium Channel Blockers - pharmacology ; Cell Division - drug effects ; Chemotherapy ; Cyclosporine - pharmacology ; Dexniguldipine-HCl ; Dihydropyridines - pharmacology ; Doxorubicin - pharmacology ; Drug Resistance, Multiple ; Etoposide - pharmacology ; Humans ; Kinetics ; Mathematics ; Medical sciences ; Multidrug resistance ; P-glycoprotein ; Pharmacology. Drug treatments ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Tritium - metabolism ; Tumor Cells, Cultured ; Vinblastine - metabolism ; Vincristine - pharmacology</subject><ispartof>European journal of pharmacology, 1994-12, Vol.288 (1), p.105-114</ispartof><rights>1994</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-a2a57560efc48ce44882b72e1050cf6d886bcfb0ccdafba25eeba2699556e2ed3</citedby><cites>FETCH-LOGICAL-c386t-a2a57560efc48ce44882b72e1050cf6d886bcfb0ccdafba25eeba2699556e2ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3401141$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7705462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Malkhandi, Joy</creatorcontrib><creatorcontrib>Ferry, David R.</creatorcontrib><creatorcontrib>Boer, Rainer</creatorcontrib><creatorcontrib>Gekeler, Volker</creatorcontrib><creatorcontrib>Ise, Wolfgang</creatorcontrib><creatorcontrib>Keer, David J.</creatorcontrib><title>Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Cell membranes were prepared from the multidrug resistant, P-glycoprotein expressing human lymphoblastoid cell line CCRF-ADR 5000. The P-glycoprotein of these membranes possessed high affinity binding sites for [
3H]vinblastine, with a
K
d of 8 ± 2 nM and
B
max of 17 ± 8 pmol/mg of protein. The binding of [
3H]vinblastine to P-glycoprotein was not ATP-dependent, and was inhibited by cytotoxic drugs with the following potency order; vincristine > doxorubicin > etoposide. The 1,4-dihydropyridine and multidrug resistance reversing agent, dexniguldipine-HCl, inhibited binding with a
K
i value of 37 nM. The multidrug resistance reversing agent cyclosporin A, and the cytotoxics doxorubicin and etoposide did not alter the kinetics of [
3H]vinblastine dissociation from P-glycoprotein; however, the 1,4-dihydropyridines dexniguldipine-HCl and nicardipine accelerated dissociation of [
3H]vinblastine. These data suggest that P-glycoprotein possesses at least two allosterically coupled drug acceptor sites; receptor site 1 which binds vinblastine, doxorubucin, etoposide and cyclosporin A, and receptor site 2 which binds dexniguldipine-HCl and other 1,4-dihydropyridines.</description><subject>Allosteric interaction</subject><subject>Allosteric Regulation</subject><subject>Antineoplastic agents</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Binding, Competitive - drug effects</subject><subject>Biological and medical sciences</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cell Division - drug effects</subject><subject>Chemotherapy</subject><subject>Cyclosporine - pharmacology</subject><subject>Dexniguldipine-HCl</subject><subject>Dihydropyridines - pharmacology</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Resistance, Multiple</subject><subject>Etoposide - pharmacology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mathematics</subject><subject>Medical sciences</subject><subject>Multidrug resistance</subject><subject>P-glycoprotein</subject><subject>Pharmacology. Drug treatments</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Tritium - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Vinblastine - metabolism</subject><subject>Vincristine - pharmacology</subject><issn>0922-4106</issn><issn>0014-2999</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMGKFDEQhnNQ1nX1DRRyENFDa9KTpDsXYel1HWFBWfQkEtLp6rEkk4xJZtl9e9POMEcvKUh9f_HzEfKCs3eccfWe6bZtBGfqjRZvNWNcNvoROT99PyFPc_7NGNNcizNy1nVMCtWek_sruA-42fsJdxigWQ-eYqaW7mKBUKj1PuYCCR3F8AtHLDHRONMfdLX-eYdh9DaXGqQjhgnDhpZIvzYb_-DiLtUTGBZ6GG6v6eXVLZW1AnXgfX5GHs_WZ3h-nBfk-_XHb8O6ufny6fNwedO4Va9KY1srO6kYzE70DoTo-3bsWuBMMjerqe_V6OaROTfZebStBKiv0lpKBS1Mqwvy-nC31vmzh1zMFvPSwAaI-2y6rqtwrysoDqBLMecEs9kl3Nr0YDgzi2Sz2DSLTaOF-SfZLLGXx_v7cQvTKXQ0XPevjnubnfVzssFhPmErwTgXvGIfDhhUF3cIyWSHEBxMmMAVM0X8f4-_p6uaXA</recordid><startdate>19941215</startdate><enddate>19941215</enddate><creator>Malkhandi, Joy</creator><creator>Ferry, David R.</creator><creator>Boer, Rainer</creator><creator>Gekeler, Volker</creator><creator>Ise, Wolfgang</creator><creator>Keer, David J.</creator><general>Elsevier B.V</general><general>Elsevier</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>19941215</creationdate><title>Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells</title><author>Malkhandi, Joy ; Ferry, David R. ; Boer, Rainer ; Gekeler, Volker ; Ise, Wolfgang ; Keer, David J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-a2a57560efc48ce44882b72e1050cf6d886bcfb0ccdafba25eeba2699556e2ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Allosteric interaction</topic><topic>Allosteric Regulation</topic><topic>Antineoplastic agents</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Binding, Competitive - drug effects</topic><topic>Biological and medical sciences</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cell Division - drug effects</topic><topic>Chemotherapy</topic><topic>Cyclosporine - pharmacology</topic><topic>Dexniguldipine-HCl</topic><topic>Dihydropyridines - pharmacology</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Resistance, Multiple</topic><topic>Etoposide - pharmacology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Mathematics</topic><topic>Medical sciences</topic><topic>Multidrug resistance</topic><topic>P-glycoprotein</topic><topic>Pharmacology. Drug treatments</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Tritium - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Vinblastine - metabolism</topic><topic>Vincristine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Malkhandi, Joy</creatorcontrib><creatorcontrib>Ferry, David R.</creatorcontrib><creatorcontrib>Boer, Rainer</creatorcontrib><creatorcontrib>Gekeler, Volker</creatorcontrib><creatorcontrib>Ise, Wolfgang</creatorcontrib><creatorcontrib>Keer, David J.</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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Malkhandi, Joy</au><au>Ferry, David R.</au><au>Boer, Rainer</au><au>Gekeler, Volker</au><au>Ise, Wolfgang</au><au>Keer, David J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1994-12-15</date><risdate>1994</risdate><volume>288</volume><issue>1</issue><spage>105</spage><epage>114</epage><pages>105-114</pages><issn>0922-4106</issn><issn>0014-2999</issn><abstract>Cell membranes were prepared from the multidrug resistant, P-glycoprotein expressing human lymphoblastoid cell line CCRF-ADR 5000. The P-glycoprotein of these membranes possessed high affinity binding sites for [
3H]vinblastine, with a
K
d of 8 ± 2 nM and
B
max of 17 ± 8 pmol/mg of protein. The binding of [
3H]vinblastine to P-glycoprotein was not ATP-dependent, and was inhibited by cytotoxic drugs with the following potency order; vincristine > doxorubicin > etoposide. The 1,4-dihydropyridine and multidrug resistance reversing agent, dexniguldipine-HCl, inhibited binding with a
K
i value of 37 nM. The multidrug resistance reversing agent cyclosporin A, and the cytotoxics doxorubicin and etoposide did not alter the kinetics of [
3H]vinblastine dissociation from P-glycoprotein; however, the 1,4-dihydropyridines dexniguldipine-HCl and nicardipine accelerated dissociation of [
3H]vinblastine. These data suggest that P-glycoprotein possesses at least two allosterically coupled drug acceptor sites; receptor site 1 which binds vinblastine, doxorubucin, etoposide and cyclosporin A, and receptor site 2 which binds dexniguldipine-HCl and other 1,4-dihydropyridines.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>7705462</pmid><doi>10.1016/0922-4106(94)90015-9</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0922-4106 |
| ispartof | European journal of pharmacology, 1994-12, Vol.288 (1), p.105-114 |
| issn | 0922-4106 0014-2999 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_77799589 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present); Alma/SFX Local Collection |
| subjects | Allosteric interaction Allosteric Regulation Antineoplastic agents ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Binding, Competitive - drug effects Biological and medical sciences Calcium Channel Blockers - pharmacology Cell Division - drug effects Chemotherapy Cyclosporine - pharmacology Dexniguldipine-HCl Dihydropyridines - pharmacology Doxorubicin - pharmacology Drug Resistance, Multiple Etoposide - pharmacology Humans Kinetics Mathematics Medical sciences Multidrug resistance P-glycoprotein Pharmacology. Drug treatments Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Tritium - metabolism Tumor Cells, Cultured Vinblastine - metabolism Vincristine - pharmacology |
| title | Dexniguldipine-HCl is a potent allosteric inhibitor of [ 3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T01%3A23%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dexniguldipine-HCl%20is%20a%20potent%20allosteric%20inhibitor%20of%20%5B%203H%5Dvinblastine%20binding%20to%20P-glycoprotein%20of%20CCRF%20ADR%205000%20cells&rft.jtitle=European%20journal%20of%20pharmacology&rft.au=Malkhandi,%20Joy&rft.date=1994-12-15&rft.volume=288&rft.issue=1&rft.spage=105&rft.epage=114&rft.pages=105-114&rft.issn=0922-4106&rft_id=info:doi/10.1016/0922-4106(94)90015-9&rft_dat=%3Cproquest_cross%3E77799589%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=77799589&rft_id=info:pmid/7705462&rft_els_id=0922410694900159&rfr_iscdi=true |