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Inhibition of K+ Efflux and Dehydration of Sickle Cells by [(Dihydroindenyl)oxy]alkanoic Acid: An Inhibitor of the K+ Cl- Cotransport System

Inhibition of K+ Efflux and Dehydration of Sickle Cells by [(Dihydroindenyl)oxy]alkanoic Acid: An Inhibitor of the K+ Cl- Cotransport System

D Vitoux, O Olivieri, R P Garay, E J Cragoe Jr, F Galacteros, Y Beuzard

Proc Natl Acad Sci U S A. 1989 Jun;86(11):4273-6.

PMID: 2726772

Abstract:

[(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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP81166474	R-(+)-DIOA		81166-47-4	Price

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