Document Detail


Fluoxetine inhibits K(+) transport pathways (K(+) efflux, Na(+)-K(+)-2Cl(-) cotransport, and Na(+) pump) underlying volume regulation in corneal endothelial cells.
MedLine Citation:
PMID:  10485996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied regulatory volume responses of cultured bovine corneal endothelial cells (CBCEC) using light scattering. We assessed the contributions of fluoxetine (Prozac) and bumetanide-sensitive membrane ion transport pathways to such responses by determining K(+) efflux and influx. Cells swollen by a 20% hypo-osmotic solution underwent a regulatory volume decrease (RVD) response, which after 6 min restored relative cell volume by 98%. Fluoxetine inhibited RVD recovery; 20 microM by 26%, and 50 microM totally. Fluoxetine had a triphasic effect on K(+) efflux; from 20 to 100 microM it inhibited efflux 2-fold, whereas at higher concentrations the efflux first increased to 1.5-fold above the control value, and then decreased again. Cells shrunk by a 20% hyperosmotic solution underwent a regulatory volume increase (RVI) which also after 6 min restored the cell volume by 99%. Fluoxetine inhibited RVI; 20 microM by 25%, and 50 microM completely. Bumetanide (1 microM) inhibited RVI by 43%. In a Cl(-)-free medium, fluoxetine (50-500 microM) progressively inhibited bumetanide-insensitive K(+) influx. The inhibitions of RVI and K(+) influx induced by fluoxetine 20 to 50 microM were similar to those induced by 1 microM bumetanide and by Cl(-)-free medium. A computer simulation suggests that fluoxetine can interact with the selectivity filter of K(+) channels. The data suggest that CBCEC can mediate RVD and RVI in part through increases in K(+) efflux and Na-K-2Cl cotransport (NKCC) activity. Interestingly, the data also suggest that fluoxetine at 20 to 50 microM inhibits NKCC, and at 100-1000 microM inhibits the Na(+) pump. One possible explanation for these findings is that fluoxetine could interact with K(+)-selective sites in K(+) channels, the NKC cotransporter and the Na(+) pump.
Authors:
E Hara; P S Reinach; Q Wen; P Iserovich; J Fischbarg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of membrane biology     Volume:  171     ISSN:  0022-2631     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-21     Completed Date:  1999-10-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  75-85     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bumetanide / pharmacology
Carrier Proteins / antagonists & inhibitors*
Cattle
Cell Size / drug effects
Cells, Cultured
Chlorides / metabolism
Endothelium, Corneal / cytology,  drug effects*,  metabolism*
Fluoxetine / chemistry,  metabolism,  pharmacology*
Ion Transport / drug effects
Kinetics
Models, Molecular
Molecular Conformation
Osmotic Pressure
Potassium / metabolism*
Potassium Channel Blockers
Potassium Channels / chemistry,  metabolism
Sodium / metabolism
Sodium-Potassium-Chloride Symporters
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
08918//PHS HHS; EY04795/EY/NEI NIH HHS; EY06178/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Chlorides; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Sodium-Potassium-Chloride Symporters; 28395-03-1/Bumetanide; 54910-89-3/Fluoxetine; 7440-09-7/Potassium; 7440-23-5/Sodium; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

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


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