| Trifluoperazine and dibucaine-induced inhibition of glutamate-induced mitochondrial depolarization in rat cultured forebrain neurones. | |
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MedLine Citation:
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PMID: 9384493 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Glutamate receptor activation has been previously shown to result in mitochondrial depolarization and activation of the mitochondrial permeability transition pore in cultured neurones. In this study, we characterized the effects of two putative permeability transition inhibitors, namely trifluoperazine and dibucaine, on mitochondrial depolarization in rat intact, cultured forebrain neurones. 2. Permeability transition was monitored by following mitochondrial depolarization in neurones loaded with the mitochondrial membrane potential-sensitive fluorescent indicator, JC-1. Trifluoperazine (10 20 microM) and dibucaine (50-100 microM) inhibited or delayed the onset of glutamate-induced permeability transition. 3. We also investigated the effects of trifluoperazine and dibucaine on neuronal recovery from glutamate-induced Ca2+ loads. Trifluoperazine affected Ca2+ recovery in a manner similar to the mitochondrial Na+/Ca2+ exchange inhibitor, CGP-37157, while dibucaine had no apparent effect on Ca2+ recovery. Therefore, inhibition of permeability transition does not appear to be involved in Ca2+ recovery from glutamate-induced Ca2+ loads. 4. Trifluoperazine and dibucaine did not inhibit [3H]-dizocilpine binding at the concentrations that prevented mitochondrial depolarization. 5. These studies suggest that trifluoperazine and dibucaine inhibit permeability transition in intact neurones. Trifluoperazine also appears to inhibit mitochondrial Na+/Ca2+ exchange. These drugs should prove to be valuable tools in the further study of the role of mitochondrial permeability transition in glutamate-induced neuronal death. |
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Authors:
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K R Hoyt; T A Sharma; I J Reynolds |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: British journal of pharmacology Volume: 122 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 1997 Nov |
Date Detail:
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Created Date: 1998-09-24 Completed Date: 1998-09-24 Revised Date: 2008-11-20 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 803-8 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261, U.S.A. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzimidazoles Calcium / metabolism Carbocyanines Cells, Cultured Clonazepam / analogs & derivatives, pharmacology Dibucaine / metabolism, pharmacology* Dizocilpine Maleate / metabolism Fluorescent Dyes Fluorometry Glutamic Acid / physiology* Membrane Potentials / drug effects Mitochondria / drug effects*, physiology Neurons / cytology, drug effects* Prosencephalon / cytology, drug effects*, metabolism Rats Rats, Sprague-Dawley Sodium-Calcium Exchanger / antagonists & inhibitors Thiazepines / pharmacology Trifluoperazine / metabolism, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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NS 34138/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzimidazoles; 0/Carbocyanines; 0/Fluorescent Dyes; 0/Sodium-Calcium Exchanger; 0/Thiazepines; 117-89-5/Trifluoperazine; 1622-61-3/Clonazepam; 21527-78-6/5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; 56-86-0/Glutamic Acid; 7440-70-2/Calcium; 75450-34-9/CGP 37157; 77086-22-7/Dizocilpine Maleate; 85-79-0/Dibucaine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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