| Isovaleric, methylmalonic, and propionic acid decrease anesthetic EC50 in tadpoles, modulate glycine receptor function, and interact with the lipid 1,2-dipalmitoyl-Sn-glycero-3-phosphocholine. | |
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MedLine Citation:
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PMID: 19372333 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Elevated concentrations of isovaleric (IVA), methylmalonic (MMA), and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses. First, that these metabolites would have anesthetic-sparing effects, possibly being anesthetics by themselves. Second, that these compounds would modulate glycine and gamma-aminobutyric acid (GABA(A)) receptor function, increasing chloride currents through these channels as potent clinical inhaled anesthetics do. Third, that these compounds would affect physical properties of lipids. METHODS: Anesthetic EC(50)s were measured in Xenopus laevis tadpoles. Glycine and GABA(A) receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. Pressure-area isotherms of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were measured with and without added organic acids. RESULTS: IVA acid was an anesthetic in tadpoles, whereas MMA and propionic acid decreased isoflurane's EC(50) by half. All three organic acids concentration-dependently increased current through alpha(1) glycine receptors. There were minimal effects on alpha(1)beta(2)gamma(2s) GABA(A) receptors. The organic acids increased total lateral pressure (surface pressure) of DPPC monolayers, including at mean molecular areas typical of bilayers. CONCLUSION: IVA, MMA, and propionic acid have anesthetic effects in tadpoles, positively modulate glycine receptor function and affect physical properties of DPPC monolayers. |
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Authors:
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Yun Weng; Tienyi Theresa Hsu; Jing Zhao; Stefanie Nishimura; Gerald G Fuller; James M Sonner |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 108 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-17 Completed Date: 2009-04-30 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 1538-45 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143-0464, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1,2-Dipalmitoylphosphatidylcholine
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metabolism* Anesthetics, Inhalation / pharmacology* Animals Cell Membrane / drug effects*, metabolism Chlorides / metabolism Dose-Response Relationship, Drug Female Isoflurane / pharmacology* Larva / drug effects, metabolism Membrane Potentials Methylmalonic Acid / pharmacology* Mutation Pentanoic Acids / pharmacology* Pressure Propionic Acids / pharmacology* Receptors, GABA-A / metabolism Receptors, Glycine / drug effects*, genetics, metabolism Surface Properties Xenopus laevis |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM069379/GM/NIGMS NIH HHS; R01 GM069379-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Inhalation; 0/Chlorides; 0/Pentanoic Acids; 0/Propionic Acids; 0/Receptors, GABA-A; 0/Receptors, Glycine; 0/glycine receptor alpha1; 2644-64-6/1,2-Dipalmitoylphosphatidylcholine; 26675-46-7/Isoflurane; 503-74-2/isovaleric acid; 516-05-2/Methylmalonic Acid; 79-09-4/propionic acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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