Evidence for multidrug resistance-1 P-glycoprotein-dependent regulation of cellular ATP permeability.
J Membr Biol
; 183(3): 165-73, 2001 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-11696858
ABSTRACT
The mechanisms responsible for regulating epithelial ATP permeability and purinergic signaling are not well defined. Based on the observations that members of the ATP-binding cassette (ABC)1 family of proteins may contribute to ATP release, the purpose of these studies was to assess whether multidrug resistance-1 (MDR1) proteins are involved in ATP release from HTC hepatoma cells. Using a bioluminescence assay to detect extracellular ATP, increases in cell volume increased ATP release approximately 3-fold. The MDR1 inhibitors cyclosporine A (10 microm) and verapramil (10 microm) inhibited ATP release by 69% and 62%, respectively (p < 0.001). Similarly, in whole-cell patch-clamp recordings, intracellular dialysis with C219 antibodies to inhibit MDR1 decreased ATP-dependent volume-sensitive Cl- current density from -33.1 +/- 12.5 pA/pF to -2.0 +/- 0.3 pA/pF (-80 mV, p < or = 0.02). In contrast, overexpression of MDR1 in NIH 3T3 cells increased ATP release rates. Inhibition of ATP release by Gd3+ had no effect on transport of the MDR1 substrate rhodamine-123; and alteration of MDR1-substrate selectivity by mutation of G185 to V185 had no effect on ATP release. Since the effects of P-glycoproteins on ATP release can be dissociated from P-glycoprotein substrate transport, MDR1 is not likely to function as an ATP channel, but instead serves as a potent regulator of other cellular ATP transport pathways.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade da Membrana Celular
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Trifosfato de Adenosina
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Cloretos
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Subfamília B de Transportador de Cassetes de Ligação de ATP
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Membr Biol
Ano de publicação:
2001
Tipo de documento:
Article