Chloroquine, a novel inhibitor of amino acid transport by rat renal brush border membrane vesicles
Identifieur interne : 002B77 ( Main/Exploration ); précédent : 002B76; suivant : 002B78Chloroquine, a novel inhibitor of amino acid transport by rat renal brush border membrane vesicles
Auteurs : R. W. Chesney [États-Unis] ; A. M. Budreau [États-Unis]Source :
- Amino Acids [ 0939-4451 ] ; 1995-06-01.
English descriptors
- KwdEn :
- Teeft :
- Acid, Amino, Amino acid, Amino acid transport, Amino acid uptake, Amino acids, Bbmv, Budreau, Chesney, Chloroquine, Chloroquine inhibition, Cystine, Cystinotic, Cystinotic fibroblasts, Efflux, Fibroblast, Further studies, Glycine, Initial rate, Intracellular, Lung slices, Lymphoblastoid cells, Membrane, Neutral acids, Poole, Renal, Renal bbmv transport, Renal brush border membrane vesicles, Several concentrations, Taurine, Taurine accumulation, Taurine diet, Taurine efflux, Taurine transport, Taurine uptake, Transporter, Triplicate, Uptake, Vesicle, Zelikovic.
Abstract
Summary: Chloroquine is an antimalarial and antirheumatic lysosomotropic drug which inhibits taurine uptake into and increases efflux from cultured human lymphoblastoid cells. It inhibits taurine uptake by rat lung slices and affects the uptake and release of cystine from cystinotic fibroblasts. Speculations on its mode of action include a proton gradient effect, a non-specific alteration in membrane integrity, and membrane stabilization. In this study, the effect of chloroquine on the uptake of several amino acids by rat renal brush border membrane vesicles (BBMV) was examined. Chloroquine significantly inhibited the secondary active, NaCl-dependent component of 10µM taurine uptake at all concentrations tested, but did not change equilibrium values. Analysis of these data indicated that the inhibition was non-competitive. Taurine uptake was reduced at all osmolarities tested, but inhibition was greatest at the lowest osmolarity. Taurine efflux was not affected by chloroquine, nor was the NaCl-independent diffusional component of taurine transport. Chloroquine (1 mM) inhibited uptake of the imino acids L-proline and glycine, and the dibasic amino acid L-lysine. It inhibited the uptake of D-glucose, but not the neutralα-amino acids L-alanine or L-methionine. Uptake of the dicarboxylic amino acids, L-glutamic acid and L-aspartic acid, was slightly enhanced. With regard to amino acid uptake by BBMV, these findings may support some of the currently proposed mechanisms of the action of chloroquine but further studies are indicated to determine why it affects the initial rate of active amino acid transport.
Url:
DOI: 10.1007/BF00806488
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">Summary: Chloroquine is an antimalarial and antirheumatic lysosomotropic drug which inhibits taurine uptake into and increases efflux from cultured human lymphoblastoid cells. It inhibits taurine uptake by rat lung slices and affects the uptake and release of cystine from cystinotic fibroblasts. Speculations on its mode of action include a proton gradient effect, a non-specific alteration in membrane integrity, and membrane stabilization. In this study, the effect of chloroquine on the uptake of several amino acids by rat renal brush border membrane vesicles (BBMV) was examined. Chloroquine significantly inhibited the secondary active, NaCl-dependent component of 10µM taurine uptake at all concentrations tested, but did not change equilibrium values. Analysis of these data indicated that the inhibition was non-competitive. Taurine uptake was reduced at all osmolarities tested, but inhibition was greatest at the lowest osmolarity. Taurine efflux was not affected by chloroquine, nor was the NaCl-independent diffusional component of taurine transport. Chloroquine (1 mM) inhibited uptake of the imino acids L-proline and glycine, and the dibasic amino acid L-lysine. It inhibited the uptake of D-glucose, but not the neutralα-amino acids L-alanine or L-methionine. Uptake of the dicarboxylic amino acids, L-glutamic acid and L-aspartic acid, was slightly enhanced. With regard to amino acid uptake by BBMV, these findings may support some of the currently proposed mechanisms of the action of chloroquine but further studies are indicated to determine why it affects the initial rate of active amino acid transport.</div>
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