| Screening of gap junction antagonists on dye coupling in the rabbit retina. | |
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MedLine Citation:
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PMID: 17711600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Feng Pan; Stephen L Mills; Stephen C Massey |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-08-22 |
Journal Detail:
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Title: Visual neuroscience Volume: 24 ISSN: 0952-5238 ISO Abbreviation: Vis. Neurosci. Publication Date: 2007 Jul-Aug |
Date Detail:
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Created Date: 2007-09-28 Completed Date: 2007-11-20 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8809466 Medline TA: Vis Neurosci Country: England |
Other Details:
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Languages: eng Pagination: 609-18 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology and Visual Science, University of Texas Medical School at Houston, Houston, Texas 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Animals Biotin / analogs & derivatives, metabolism Boron Compounds / pharmacology Coloring Agents Cyclooxygenase Inhibitors / pharmacology Diffusion Drug Evaluation, Preclinical Female Gap Junctions / drug effects* Glycyrrhetinic Acid / pharmacology Immunohistochemistry Male Meclofenamic Acid / pharmacology Mefloquine / pharmacology Microscopy, Confocal Nerve Net / cytology, drug effects, physiology Rabbits Retina / cytology, drug effects* |
| Grant Support | |
ID/Acronym/Agency:
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EY 06515/EY/NEI NIH HHS; EY 10121/EY/NEI NIH HHS; EY 10608/EY/NEI NIH HHS; R01 EY010121-12/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Boron Compounds; 0/Coloring Agents; 0/Cyclooxygenase Inhibitors; 0/neurobiotin; 471-53-4/Glycyrrhetinic Acid; 53230-10-7/Mefloquine; 58-85-5/Biotin; 644-62-2/Meclofenamic Acid; 83075-94-9/diphenylborate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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