Document Detail


Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel.
MedLine Citation:
PMID:  19234350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: There is a correlation between cell volume changes and changes in the rate of aqueous humor outflow; agents that decrease trabecular meshwork (TM) cell volume increase the rate of aqueous humor outflow. This study investigated the effects of the nitric oxide (NO)-independent activators of soluble guanylate cyclase (sGC), YC-1, and BAY-58-2667 on TM cell volume and the signal transduction pathways and ion channel involved. METHODS: Cell volume was measured with the use of calcein AM fluorescent dye, detected by confocal microscopy. Inhibitors and activators of sGC, 3',5'-cyclic guanosine monophosphate (cGMP), protein kinase G (PKG), and the BK(Ca) channel were used to characterize their involvement in the YC-1- and BAY-58-2667-induced regulation of TM cell volume. cGMP was assayed by an enzyme immunoassay. RESULTS: YC-1 (10 nM-200 microM) and BAY-58-2667 (10 nM-100 microM) each elicited a biphasic effect on TM cell volume. YC-1 (1 microM) increased TM cell volume, but higher concentrations decreased TM cell volume. Similarly, BAY-58-2667 (100 nM) increased TM cell volume, but higher concentrations decreased cell volume. The YC-1-induced cell volume decrease was mimicked by 8-Br-cGMP and abolished by the sGC inhibitor ODQ, the PKG inhibitor (RP)-8-Br-PET-cGMP-S, and the BK(Ca) channel inhibitor IBTX. The BAY-58-2667-induced cell volume decrease was mimicked by 8-Br-cGMP and was abolished by the PKG inhibitor and the BK(Ca) channel inhibitor. Unlike the YC-1 response, ODQ potentiated the BAY-58-2667-induced decreases in cell volume. CONCLUSIONS: These data suggest that the NO-independent decrease in TM cell volume is mediated by the sGC/cGMP/PKG pathway and involves K(+) efflux.
Authors:
William M Dismuke; Najam A Sharif; Dorette Z Ellis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-21
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  50     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-24     Completed Date:  2009-07-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3353-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Benzoic Acids / pharmacology*
Cell Size / drug effects*
Cyclic GMP / analogs & derivatives,  metabolism,  pharmacology
Cyclic GMP-Dependent Protein Kinases / metabolism
Enzyme Activators
Enzyme Inhibitors / pharmacology
Fluoresceins / metabolism
Fluorescent Dyes / metabolism
Guanylate Cyclase / metabolism*
Humans
Indazoles / pharmacology*
Large-Conductance Calcium-Activated Potassium Channels / metabolism*
Microscopy, Confocal
Nitric Oxide / metabolism*
Oxadiazoles / pharmacology
Quinoxalines / pharmacology
Trabecular Meshwork / cytology*,  metabolism
Chemical
Reg. No./Substance:
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Benzoic Acids; 0/Enzyme Activators; 0/Enzyme Inhibitors; 0/Fluoresceins; 0/Fluorescent Dyes; 0/Indazoles; 0/Large-Conductance Calcium-Activated Potassium Channels; 0/Oxadiazoles; 0/Quinoxalines; 10102-43-9/Nitric Oxide; 148504-34-1/calcein AM; 154453-18-6/3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; 31356-94-2/8-bromocyclic GMP; 329773-35-5/BAY 58-2667; 7665-99-8/Cyclic GMP; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 4.6.1.2/Guanylate Cyclase

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


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