Characterization of multidrug resistance P-glycoprotein transport function with an organotechnetium cation

Journal Article · Tue Sep 26 04:00:00 EDT 1995 · Biochemistry (Eaton)

DOI:https://doi.org/10.1021/bi00038a015· OSTI ID:273887

Piwnica-Worms, D; Vallabhaneni, V R ^[1]; Kronauge, J F ^[2]

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1. Washington Univ. Medical School, St. Louis, MO (United States)
2. Harvard Medical School, Boston, MA (United States); and others

Multidrug resistance (MDR) in mammalian cells and tumors is associated with overexpression of an {approximately}170 integral membrane efflux transporter, the MDR1 P-glycoprotein. Hexakis(2-methoxyisobutyl isonitrile) technetium(I) (Tc-SESTAMIBI), a {gamma}-emitting lipophilic cationic metallopharmaceutical, has recently been shown to be a P-glycoprotein transport substrate. Exploiting the negligible lipid membrane adsorption properties of this organometallic substrate, we studied the transport kinetics, pharmacology, drug binding, and modulation of P-glycoprotein in cell preparations derived from a variety of species and selection strategies, including SW-1573, V79, Alex, and CHO drug-sensitive cells and in 77A, LZ-8, and Alex/A.5 MDR cells. Rapid cell accumulation (T{sub 1/2} {approx} 6 min) of the agent to a steady state was observed which was inversely proportional to immunodetectable levels of P-glycoprotein. Many MDR cytotoxic agents inhibited P-glycoprotein-mediated Tc-SESTAMIBI efflux, thereby enhancing organometallic cation accumulation. 70 refs., 7 figs., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 273887
• Journal Information: Biochemistry (Eaton), Journal Name: Biochemistry (Eaton) Journal Issue: 38 Vol. 34; ISSN 0006-2960; ISSN BICHAW
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ACTINOMYCIN
ADSORPTION
ANIMAL CELLS
BIOCHEMISTRY
CELL MEMBRANES
CHEMOTHERAPY
COLCHICINE
DOXORUBICIN
DRUGS
GLYCOPROTEINS
MEMBRANE TRANSPORT
MODULATION
NEOPLASMS
PHARMACOLOGY
PHENOTYPE
TECHNETIUM COMPOUNDS
VINBLASTINE