Document Detail

Screening of gap junction antagonists on dye coupling in the rabbit retina.
MedLine Citation:
PMID:  17711600     Owner:  NLM     Status:  MEDLINE    
Many cell types in the retina are coupled via gap junctions and so there is a pressing need for a potent and reversible gap junction antagonist. We screened a series of potential gap junction antagonists by evaluating their effects on dye coupling in the network of A-type horizontal cells. We evaluated the following compounds: meclofenamic acid (MFA), mefloquine, 2-aminoethyldiphenyl borate (2-APB), 18-alpha-glycyrrhetinic acid, 18-beta-glycyrrhetinic acid (18-beta-GA), retinoic acid, flufenamic acid, niflumic acid, and carbenoxolone. The efficacy of each drug was determined by measuring the diffusion coefficient for Neurobiotin (Mills & Massey, 1998). MFA, 18-beta-GA, 2-APB and mefloquine were the most effective antagonists, completely eliminating A-type horizontal cell coupling at a concentration of 200 muM. Niflumic acid, flufenamic acid, and carbenoxolone were less potent. Additionally, carbenoxolone was difficult to wash out and also may be harmful, as the retina became opaque and swollen. MFA, 18-beta-GA, 2-APB and mefloquine also blocked coupling in B-type horizontal cells and AII amacrine cells. Because these cell types express different connexins, this suggests that the antagonists were relatively non-selective across several different types of gap junction. It should be emphasized that MFA was water-soluble and its effects on dye coupling were easily reversible. In contrast, the other gap junction antagonists, except carbenoxolone, required DMSO to make stock solutions and were difficult to wash out of the preparation at the doses required to block coupling in A-type HCs. The combination of potency, water solubility and reversibility suggest that MFA may be a useful compound to manipulate gap junction coupling.
Feng Pan; Stephen L Mills; Stephen C Massey
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-08-22
Journal Detail:
Title:  Visual neuroscience     Volume:  24     ISSN:  0952-5238     ISO Abbreviation:  Vis. Neurosci.     Publication Date:    2007 Jul-Aug
Date Detail:
Created Date:  2007-09-28     Completed Date:  2007-11-20     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  8809466     Medline TA:  Vis Neurosci     Country:  England    
Other Details:
Languages:  eng     Pagination:  609-18     Citation Subset:  IM    
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MeSH Terms
Biotin / analogs & derivatives,  metabolism
Boron Compounds / pharmacology
Coloring Agents
Cyclooxygenase Inhibitors / pharmacology
Drug Evaluation, Preclinical
Gap Junctions / drug effects*
Glycyrrhetinic Acid / pharmacology
Meclofenamic Acid / pharmacology
Mefloquine / pharmacology
Microscopy, Confocal
Nerve Net / cytology,  drug effects,  physiology
Retina / cytology,  drug effects*
Grant Support
EY 06515/EY/NEI NIH HHS; EY 10121/EY/NEI NIH HHS; EY 10608/EY/NEI NIH HHS; R01 EY010121/EY/NEI NIH HHS; R01 EY010121-12/EY/NEI NIH HHS
Reg. No./Substance:
0/Boron Compounds; 0/Coloring Agents; 0/Cyclooxygenase Inhibitors; 0/neurobiotin; 48I5LU4ZWD/Meclofenamic Acid; 6SO6U10H04/Biotin; 83075-94-9/diphenylborate; P540XA09DR/Glycyrrhetinic Acid; TML814419R/Mefloquine

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

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