Okadaic acid inhibits activation of K-Cl cotransport in red blood cells containing hemoglobins S and C.
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.
Orringer
E P
EP
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Brockenbrough
J S
JS
Whitney
J A
JA
Glosson
P S
PS
Parker
J C
JC
D002352:Carrier Proteins / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006444:Hemoglobin C / Q000032:analysis*; D006451:Hemoglobin, Sickle / Q000032:analysis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019319:Okadaic Acid; D009994:Osmolar Concentration; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011188:Potassium / Q000037:antagonists & inhibitors / Q000097:blood; D027981:Symporters; D000096922:K Cl- Cotransporters
D002352:Carrier Proteins; D004988:Ethers, Cyclic; D006444:Hemoglobin C; D006451:Hemoglobin, Sickle; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D011188:Potassium; D027981:Symporters; D000096922:K Cl- Cotransporters