Abstract:
:The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was strongly labeled. The binding of 3H-cyclosporine diazirine analogue to P-glycoprotein was competable by excess cyclosporine A and by the nonimmunosuppressive cyclosporine H. These results suggest that cyclosporine reverses the MDR phenotype by binding directly to P-glycoprotein and that this binding is not dependent on the immunosuppressive potential of the cyclosporine derivative. The identification of P-glycoprotein as a cyclosporine binding protein has obvious implications for cancer chemotherapy.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Foxwell BM,Mackie A,Ling V,Ryffel Bsubject
Has Abstractpub_date
1989-10-01 00:00:00pages
543-6issue
4eissn
0026-895Xissn
1521-0111journal_volume
36pub_type
杂志文章abstract::Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) is a major mechanism of desensitization of these receptors. GPCR activation of GRKs involves an allosteric site on GRKs distinct from the catalytic site. Although recent studies have suggested an important role of the N- and C-termini and do...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.058115
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1996-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1994-09-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 评论,杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1984-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
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pub_type: 杂志文章
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