Drug-stimulated ATPase activity of the human P-glycoprotein.
The human multidrug resistance protein, or P-glycoprotein (Pgp), exhibits a high-capacity drug-dependent ATP hydrolytic activity that is a direct reflection of its drug transport capability. This activity is readily measured in membranes isolated from cultured insect cells infected with a baculovirus carrying the human mdr1 cDNA. The drug-stimulated ATPase activity is a useful alternative to conventional screening systems for identifying high-affinity drug substrates of the Pgp with potential clinical value as chemosensitizers for tumor cells that have become drug resistant. Using this assay system, a variety of drugs have been directly shown to interact with the Pgp. Many of the drugs stimulate the Pgp ATPase activity, but certain drugs bind tightly to the drug-binding site of the Pgp without eliciting ATP hydrolysis. Either class of drugs may be useful as chemosensitizing agents. The baculovirus/insect cell Pgp ATPase assay system may also facilitate future studies of the molecular structure and mechanism of the Pgp.
Scarborough
G A
GA
Department of Pharmacology, University of North Carolina, Chapel Hill 27599, USA.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D016367:Baculoviridae; D018076:DNA, Complementary / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006801:Humans; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases