| Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels. | |
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MedLine Citation:
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PMID: 18822352 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased hydrostatic pressure can damage neurons, although the mechanisms linking pressure to neurochemical imbalance or cell injury are not fully established. Throughout the body, mechanical perturbations such as shear stress, cell stretching, or changes in pressure can lead to excessive release of ATP. It is thus possible that increased pressure across neural tissues triggers an elevated release of ATP into extracellular space. As stimulation of the P2X(7) receptor for ATP on retinal ganglion cells leads to elevation of intracellular calcium and excitotoxic death, we asked whether increased levels of extracellular ATP accompanied an elevation in pressure across the retina. The hydrostatic pressure surrounding bovine retinal eyecups was increased and the ATP content of the vitreal compartment adjacent to the retina was determined. A step increase of only 20 mm Hg induced a threefold increase in the vitreal ATP concentration. The ATP levels correlated closely with the degree of pressure increase over 20-100 mm Hg. The increase was transient at lower pressures but sustained at higher pressures. The rise in vitreal ATP was the same regardless of whether nitrogen or air was used to increase pressure, implying changes in oxygen partial pressure did not contribute. Lactate dehydrogenase activity was not affected by pressure, ruling out a substantial contribution from cell lysis. The ATP increase was largely inhibited by either 30 muM 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) or 10 muM carbenoxolone (CBX). While this pharmacological profile is consistent with physiological release of ATP through pannexins hemichannels, a contribution from anion channels, vesicular release or other mechanisms cannot be ruled out. In conclusion, a step elevation in pressure leads to a physiologic increase in the levels of extracellular ATP bathing retinal neurons. This excess extracellular ATP may link increased pressure to the death of ganglion cells in acute glaucoma, and suggests a possible role for ATP in the neuronal damage accompanying increased intracranial pressure. |
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Authors:
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D Reigada; W Lu; M Zhang; C H Mitchell |
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: 2008-08-27 |
Journal Detail:
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Title: Neuroscience Volume: 157 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-18 Completed Date: 2009-04-09 Revised Date: 2012-02-23 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 396-404 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism* Analysis of Variance Angiogenesis Inhibitors / pharmacology Animals Carbenoxolone / pharmacology Cattle Eye / cytology Intraocular Pressure / physiology* L-Lactate Dehydrogenase / metabolism Mefloquine / pharmacology Nitrobenzoates / pharmacology Retina / drug effects, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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EY001583/EY/NEI NIH HHS; EY013434/EY/NEI NIH HHS; EY015537/EY/NEI NIH HHS; R01 EY013434-06A2/EY/NEI NIH HHS; R01 EY013434-10/EY/NEI NIH HHS; R01 EY015537-04/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Nitrobenzoates; 107254-86-4/5-nitro-2-(3-phenylpropylamino)benzoic acid; 53230-10-7/Mefloquine; 56-65-5/Adenosine Triphosphate; 5697-56-3/Carbenoxolone; EC 1.1.1.27/L-Lactate Dehydrogenase |
| Comments/Corrections | |
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