Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies.

Article Details

Citation

Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr

Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies.

Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9.

PubMed ID
14985103 [ View in PubMed
]
Abstract

P-glycoprotein (Pgp) is one of the ABC transporters responsible for the multidrug resistance of cancer cells. The conformational changes of Pgp that occur in the presence of substrates/modulators or ATP depletion are accompanied by the up-shift of UIC2 monoclonal antibody (mAb) binding. In the case of cyclosporin A, vinblastine or valinomycin, this up-shift was found to be concomitant with the near-complete suppression of labeling with other mAbs specific for Pgp epitopes overlapping with UIC2, while pre-treatment with verapamil or Tween 80 brings about a modest suppression. Here we have extended these observations to 44 Pgp interacting agents, and found that only 8 fall into the cyclosporin-like category, inducing a conformational state characterized by the complete UIC2 dominance. The rest of the drugs either did not affect antibody competition or had a modest effect. Thus, Pgp substrates/modulators can be classified into distinct modalities based on the conformational change they elicit.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AmsacrineATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
BenzocaineATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
DactinomycinATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
DesipramineATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
EtoposideATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
GenisteinATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
Gramicidin DATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
HaloperidolATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImipramineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Details
IvermectinATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
KetoconazoleATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
LidocaineATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
MibefradilATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
NifedipineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inducer
Details
PaclitaxelATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
PrednisoneATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inducer
Details
ProgesteroneATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
PropranololATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Details
QuercetinATP-dependent translocase ABCB1ProteinHumans
Unknown
Inhibitor
Details
QuinidineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
QuinineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
ReserpineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
SirolimusATP-dependent translocase ABCB1ProteinHumans
No
Substrate
Inhibitor
Inducer
Details
VinblastineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
VincristineATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details