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
AmsacrineP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
BenzocaineP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
DactinomycinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
DesipramineP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
EtoposideP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
GenisteinP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
Gramicidin DP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
HaloperidolP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImipramineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details
IvermectinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
KetoconazoleP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
LidocaineP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
MibefradilP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
NifedipineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inducer
Details
PaclitaxelP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
PrednisoneP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inducer
Details
ProgesteroneP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
PropranololP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details
QuercetinP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
QuinidineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
QuinineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
ReserpineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
SirolimusP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Inducer
Details
VinblastineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
VincristineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details