Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-22
pubmed:abstractText
P-glycoprotein is a plasma membrane protein of mammalian cells that confers multidrug resistance by acting as a broad-specificity, ATP-dependent efflux transporter of diverse lipophilic neutral or cationic compounds. Previously, we identified two positively cooperative drug-binding sites of P-glycoprotein involved in transport [Shapiro, A. B. & Ling, V. (1997) Eur. J. Biochem. 250, 130-137]. The H site is selective for Hoechst 33342 and colchicine. The R site is selective for rhodamine 123 and anthracyclines. Substrate binding to one site stimulates transport by the other. In this paper, we show that prazosin and progesterone stimulate the transport of both Hoechst 33342 and rhodamine 123. Rhodamine 123 and prazosin (or progesterone) in combination stimulate Hoechst 33342 transport in an additive manner. In contrast, Hoechst 33342 and either prazosin or progesterone interfere with each other, so that the stimulatory effect of the combination on rhodamine 123 transport is less than that of each individually. Non-P-glycoprotein-specific effects of prazosin on membrane fluidity and permeability were excluded. These results indicate the existence of a third drug-binding site on P-glycoprotein with a positive allosteric effect on drug transport by the H and R sites. This allosteric site appears to be one of the sites of photoaffinity labeling of P-glycoprotein by [125I]iodoarylazidoprazosin [Safa, A. R., Agresti, M., Bryk, D. & Tamai, I. (1994) Biochemistry 33, 256-265] and is likely not to be capable of drug transport.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
841-50
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed-meshheading:10092872-Allosteric Site, pubmed-meshheading:10092872-Animals, pubmed-meshheading:10092872-Benzimidazoles, pubmed-meshheading:10092872-Binding Sites, pubmed-meshheading:10092872-Biological Transport, pubmed-meshheading:10092872-CHO Cells, pubmed-meshheading:10092872-Cell Membrane, pubmed-meshheading:10092872-Cricetinae, pubmed-meshheading:10092872-Fluorescent Dyes, pubmed-meshheading:10092872-Flupenthixol, pubmed-meshheading:10092872-Haloperidol, pubmed-meshheading:10092872-Molecular Structure, pubmed-meshheading:10092872-P-Glycoprotein, pubmed-meshheading:10092872-Prazosin, pubmed-meshheading:10092872-Progesterone, pubmed-meshheading:10092872-Propranolol, pubmed-meshheading:10092872-Protein Binding, pubmed-meshheading:10092872-Rhodamine 123, pubmed-meshheading:10092872-Spiperone
pubmed:year
1999
pubmed:articleTitle
Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site.
pubmed:affiliation
British Columbia Cancer Research Centre, Vancouver, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't