PMID- 7130394 OWN - NLM STAT- MEDLINE DCOM- 19821216 LR - 20190606 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 70 IP - 5 DP - 1982 Nov TI - Hydration of sickle cells using the sodium ionophore Monensin. A model for therapy. PG - 1074-80 AB - Mean cell hemoglobin concentration (MCHC) is thought to have an important influence in sickle cell disease, both through the strong dependence of sickling rates on hemoglobin S concentration, and through the profoundly limiting effect of high MCHC on the rheologic competence of oxygenated, irreversibly sickled cells (ISC). Recent studies have tested the ability of antidiuretic hormone to reduce sickle cell MCHC by reducing plasma sodium (Na) and osmolality. An alternative means of reducing MCHC is to elevate intracellular cation content, rather than to depress extracellular cation concentration. In an effort to do this, we have treated sickle cells with Monensin, an antibiotic that selectively enhances membrane Na permeability. At submicromolar concentrations, Monensin substantially reduced the MCHC of whole sickle blood and isolated ISC, causing an improvement in cell deformability. Monensin's effectiveness in producing a controlled increase in erythrocyte water content suggests that agents that selectively increase membrane Na permeability could be therapeutically useful. FAU - Clark, M R AU - Clark MR FAU - Mohandas, N AU - Mohandas N FAU - Shohet, S B AU - Shohet SB LA - eng GR - AM 16095/AM/NIADDK NIH HHS/United States GR - AM 26263/AM/NIADDK NIH HHS/United States GR - HL 20985/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Furans) RN - 0 (Hemoglobin, Sickle) RN - 0 (Ionophores) RN - 9008-00-8 (Hemoglobin C) RN - 906O0YJ6ZP (Monensin) RN - 9NEZ333N27 (Sodium) RN - RWP5GA015D (Potassium) SB - IM MH - Anemia, Sickle Cell/blood/drug therapy/genetics MH - Centrifugation, Density Gradient MH - Erythrocytes, Abnormal/*drug effects/metabolism/physiology MH - Furans/*pharmacology MH - Hemoglobin C/genetics MH - Hemoglobin, Sickle/genetics MH - Hemolysis/drug effects MH - Humans MH - Hydrogen-Ion Concentration MH - Ionophores/pharmacology/therapeutic use MH - Models, Biological MH - Monensin/*pharmacology/therapeutic use MH - Osmolar Concentration MH - Potassium/blood MH - Sodium/*blood MH - Stimulation, Chemical MH - Water-Electrolyte Balance/*drug effects PMC - PMC370320 EDAT- 1982/11/01 00:00 MHDA- 1982/11/01 00:01 PMCR- 1982/11/01 CRDT- 1982/11/01 00:00 PHST- 1982/11/01 00:00 [pubmed] PHST- 1982/11/01 00:01 [medline] PHST- 1982/11/01 00:00 [entrez] PHST- 1982/11/01 00:00 [pmc-release] AID - 10.1172/jci110695 [doi] PST - ppublish SO - J Clin Invest. 1982 Nov;70(5):1074-80. doi: 10.1172/jci110695.