Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies.
Article Details
- CitationCopy to clipboard
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
Drug Transporter Kind Organism Pharmacological Action Actions Amsacrine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Benzocaine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Dactinomycin P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Desipramine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Etoposide P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Genistein P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Gramicidin D P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Haloperidol P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Imipramine P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Ivermectin P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails Ketoconazole P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Lidocaine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Mibefradil P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Nifedipine P-glycoprotein 1 Protein Humans UnknownSubstrateInducerDetails Paclitaxel P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Prednisone P-glycoprotein 1 Protein Humans UnknownSubstrateInducerDetails Progesterone P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails Propranolol P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Quercetin P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Quinidine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Quinine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Reserpine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails Sirolimus P-glycoprotein 1 Protein Humans NoSubstrateInhibitorInducerDetails Vinblastine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails Vincristine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails