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Am J Physiol Cell Physiol 261: C591-C593, 1991;
0363-6143/91 $5.00
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AJP - Cell Physiology, Vol 261, Issue 4 C591-C593, Copyright © 1991 by American Physiological Society


ARTICLES

Okadaic acid inhibits activation of K-Cl cotransport in red blood cells containing hemoglobins S and C

E. P. Orringer, J. S. Brockenbrough, J. A. Whitney, P. S. Glosson and J. C. Parker
Department of Medicine, University of North Carolina, Chapel Hill 27599.

The sensitivity of red blood cells containing hemoglobins S and C to activation of K-Cl cotransport by osmotic swelling and acidification was reduced by okadaic acid, a specific protein phosphatase inhibitor. The dose-response curve for okadaic acid suggests its action is on a type 1 protein phosphatase. Okadaic acid has been previously shown to inhibit swelling-induced activation of K-Cl cotransport in red blood cells from rabbits, normal humans, and dogs. The present work confirms the observation that okadaic acid blunts the stimulation of K-Cl cotransport by cell swelling. The new information is that okadaic acid reduces the effects of hemoglobins S and C on the volume and pH sensitivity of K-Cl cotransport. Thus the influences of cell volume, pH, and mutant hemoglobins may all be mediated via a common mechanisms that affects the phosphorylation state, either of the K-Cl. cotransporter itself or of a protein that regulates its function.


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