Document Detail


Volume control in sickle cells is facilitated by the novel anion conductance inhibitor NS1652.
MedLine Citation:
PMID:  10688846     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A low cation conductance and a high anion conductance are characteristic of normal erythrocytes. In sickle cell anemia, the polymerization of hemoglobin S (HbS) under conditions of low oxygen tension is preceded by an increase in cation conductance. This increase in conductance is mediated in part through Ca(++)-activated K(+) channels. A net efflux of potassium chloride (KCl) leads to a decrease in intracellular volume, which in turn increases the rate of HbS polymerization. Treatments minimizing the passive transport of ions and solvent to prevent such volume depletion might include inhibitors targeting either the Ca(++)-activated K(+) channel or the anion conductance. NS1652 is an anion conductance inhibitor that has recently been developed. In vitro application of this compound lowers the net KCl loss from deoxygenated sickle cells from about 12 mmol/L cells/h to about 4 mmol/L cells/h, a value similar to that observed in oxygenated cells. Experiments performed in mice demonstrate that NS1652 is well tolerated and decreases red cell anion conductance in vivo. (Blood. 2000;95:1842-1848)
Authors:
P Bennekou; O Pedersen; A Møller; P Christophersen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Blood     Volume:  95     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-03-29     Completed Date:  2000-03-29     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1842-8     Citation Subset:  AIM; IM    
Affiliation:
August Krogh Institute, University of Copenhagen, Denmark. pbennekou@aki.ku.dk
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MeSH Terms
Descriptor/Qualifier:
Anemia, Sickle Cell / pathology*
Animals
Anions / blood*
Benzoic Acids / pharmacology*,  toxicity
Biopolymers
Cell Size / drug effects
Chloride Channels / blood,  drug effects*
Depression, Chemical
Dose-Response Relationship, Drug
Erythrocyte Membrane / drug effects*
Erythrocytes, Abnormal / drug effects*,  metabolism,  ultrastructure
Hemoglobin, Sickle / chemistry,  metabolism
Hemoglobins / metabolism
Humans
Ion Transport / drug effects
L Cells (Cell Line) / drug effects,  metabolism
Mice
Phenylurea Compounds / pharmacology*,  toxicity
Potassium Channels / blood*
Potassium Chloride / blood
Sulfates / blood
Chemical
Reg. No./Substance:
0/Anions; 0/Benzoic Acids; 0/Biopolymers; 0/Chloride Channels; 0/Hemoglobin, Sickle; 0/Hemoglobins; 0/NS 1652; 0/Phenylurea Compounds; 0/Potassium Channels; 0/Sulfates; 7447-40-7/Potassium Chloride; 9008-02-0/deoxyhemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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