| Autor: |
Vitoux, D, Olivieri, O, Garay, R P, Cragoe, E J, Galacteros, F, Beuzard, Y |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; June 1989, Vol. 86 Issue: 11 p4273-4276, 4p |
| Abstrakt: |
[(Dihydroindenyl)oxy]alkanoic acid (DIOA) was recently introduced as a potent inhibitor of the K+Cl- cotransport system without side effects on other cation transport systems [Garay, R. P., Nazaret, C., Hannaert, P.A. & Cragoe, E. J., Jr. (1988) Mol. Pharmacol. 33, 696-701]. In sickle cells, an abnormal activation of this K+Cl- cotransport system was proposed to be involved in cell K+ loss and dehydration. We found that DIOA inhibited the abnormal sickle cell K+ loss and specifically reduced sickle cell density upon stimulation of the net outward K+Cl- cotransport--i.e., low pH, hypoosmolarity, and activation by N-ethylmaleimide. DIOA opens another therapeutic approach to sickle cell disease by inhibiting cell dehydration, which favors HbS polymerization and reduces erythrocyte deformability. |
| Databáze: |
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