title: Selection and characterization of verapamil-resistant multidrug resistant cells.
abstract: Multidrug resistant cells may become acutely sensitive to the calcium channel blocker verapamil, in spite of the fact that its accumulation by these cells is negligible. We selected verapamil-resistant mutants from multidrug resistant Chinese hamster ovary cells. Levels of P-glycoprotein expression and cross-resistance profiles remained unaltered in the verapamil-resistant multidrug resistant cells. As well, a photoactive verapamil analog specifically bound to P-glycoprotein in these cells. We had previously used a photoactive anthracycline to show that calcium antagonists and several anticancer drugs bind to P-glycoprotein at overlapping or interacting sites. Verapamil and its analogues no longer inhibit the binding of either anticancer drugs or calcium channel blockers to P-glycoprotein. Sequencing of P-glycoprotein revealed that no change had occurred in the coding sequence as a result of the selection procedure.
authors.affiliation: Research Institute, Hospital for Sick Children Toronto, Ontario, Canada.
authors.forename: D F
authors.initials: DF
authors.lastname: Cano-Gauci
authors.forename: F S
authors.initials: FS
authors.lastname: Seibert
authors.forename: A R
authors.initials: AR
authors.lastname: Safa
authors.forename: J R
authors.initials: JR
authors.lastname: Riordan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000494:pharmacology; D010777:Photochemistry; D011485:Protein Binding; D014700:Verapamil / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007462:Iodobenzenes; C060588:iodomycin; D014747:Vinblastine; C041028:iodipine; D014700:Verapamil; D003630:Daunorubicin