Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog
Abstract
Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.
- Authors:
- Publication Date:
- Research Org.:
- Kagoshima Univ. (Japan)
- OSTI Identifier:
- 5438319
- Resource Type:
- Journal Article
- Journal Name:
- Mol. Pharmacol.; (United States)
- Additional Journal Information:
- Journal Volume: 33:2
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; DRUGS; BIOCHEMICAL REACTION KINETICS; GLUCOPROTEINS; LABELLING; AZIDES; INHIBITION; IODINE 125; MEMBRANE PROTEINS; PHENOTHIAZINES; TRACER TECHNIQUES; TUMOR CELLS; ANIMAL CELLS; AZINES; BETA DECAY RADIOISOTOPES; CARBOHYDRATES; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; HETEROCYCLIC COMPOUNDS; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; NITROGEN COMPOUNDS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PROTEINS; RADIOISOTOPES; REACTION KINETICS; SACCHARIDES; 550201* - Biochemistry- Tracer Techniques
Citation Formats
Akiyama, S, Cornwell, M M, Kuwano, M, Pastan, I, and Gottesman, M M. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog. United States: N. p., 1988.
Web.
Akiyama, S, Cornwell, M M, Kuwano, M, Pastan, I, & Gottesman, M M. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog. United States.
Akiyama, S, Cornwell, M M, Kuwano, M, Pastan, I, and Gottesman, M M. 1988.
"Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog". United States.
@article{osti_5438319,
title = {Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog},
author = {Akiyama, S and Cornwell, M M and Kuwano, M and Pastan, I and Gottesman, M M},
abstractNote = {Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.},
doi = {},
url = {https://www.osti.gov/biblio/5438319},
journal = {Mol. Pharmacol.; (United States)},
number = ,
volume = 33:2,
place = {United States},
year = {Mon Feb 01 00:00:00 EST 1988},
month = {Mon Feb 01 00:00:00 EST 1988}
}