Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog

Journal Article · Mon Feb 01 00:00:00 EST 1988 · Mol. Pharmacol.; (United States)

OSTI ID:5438319

Akiyama, S; Cornwell, M M; Kuwano, M; Pastan, I; Gottesman, M M

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.

• Research Organization: Kagoshima Univ. (Japan)
• OSTI ID: 5438319
• Journal Information: Mol. Pharmacol.; (United States), Vol. 33:2
• Country of Publication: United States
• Language: English

Related Subjects

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