| Quinolinic acid toxicity on orexin neurons blocked by gamma aminobutyric acid type A receptor stimulation. | |
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MedLine Citation:
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PMID: 16012340 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Selective degeneration of hypothalamic orexin neurons, a hallmark of pathology in narcolepsy patients, is in part reproduced in hypothalamic slice cultures by application of an endogenous excitotoxin quinolinic acid. Depolarized membrane potential may be responsible for the vulnerability of orexin neurons to excitotoxicity. We show that stimulation of gamma-aminobutyric acid type A receptors, which is known to hyperpolarize orexin neurons, by muscimol or isoguvacine potently inhibits quinolinic acid cytotoxicity on orexin neurons. In addition, the protective effect of gamma-aminobutyric acid and a gamma-aminobutyric acid uptake blocker nipecotic acid is abolished by a gamma-aminobutyric acid type A antagonist picrotoxin. Norepinephrine and serotonin do not provide a neuroprotective effect. Thus, GABAergic inhibitory control may be a decisive factor regulating survival of orexin neurons under excitotoxic insults. |
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Authors:
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Hiroshi Katsuki; Akinori Akaike |
Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuroreport Volume: 16 ISSN: 0959-4965 ISO Abbreviation: Neuroreport Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-13 Completed Date: 2005-10-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9100935 Medline TA: Neuroreport Country: England |
Other Details:
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Languages: eng Pagination: 1157-61 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Bicuculline / pharmacology Cell Count / methods Citalopram / pharmacology Dose-Response Relationship, Drug Drug Interactions Fluoxetine / analogs & derivatives, pharmacology GABA Agonists / pharmacology* GABA Antagonists / pharmacology Glutamate Decarboxylase / metabolism Hypothalamus / cytology Immunohistochemistry / methods Intracellular Signaling Peptides and Proteins / metabolism* Magnesium / metabolism Neurons / drug effects*, metabolism Neuropeptides / metabolism* Nipecotic Acids / pharmacology Norepinephrine / antagonists & inhibitors, pharmacology Organophosphorus Compounds / pharmacology Picrotoxin / pharmacology Quinolinic Acid / toxicity* Rats Rats, Wistar Receptors, G-Protein-Coupled Receptors, GABA-A / physiology* Receptors, Neuropeptide Serotonin / pharmacology Serotonin Uptake Inhibitors / pharmacology gamma-Aminobutyric Acid / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/GABA Agonists; 0/GABA Antagonists; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Nipecotic Acids; 0/Organophosphorus Compounds; 0/Receptors, G-Protein-Coupled; 0/Receptors, GABA-A; 0/Receptors, Neuropeptide; 0/Serotonin Uptake Inhibitors; 0/orexin receptors; 0/orexins; 124-87-8/Picrotoxin; 149184-21-4/CGP 54626; 485-49-4/Bicuculline; 498-95-3/nipecotic acid; 50-67-9/Serotonin; 51-41-2/Norepinephrine; 54910-89-3/Fluoxetine; 56-12-2/gamma-Aminobutyric Acid; 57226-61-6/nisoxetine; 59729-33-8/Citalopram; 7439-95-4/Magnesium; 89-00-9/Quinolinic Acid; EC 4.1.1.15/Glutamate Decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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