| Glycine enhances microglial intracellular calcium signaling. A role for sodium-coupled neutral amino acid transporters. | |
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MedLine Citation:
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PMID: 21350800 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The inhibitory neurotransmitter glycine is known to enhance microglial nitric oxide production. However, up to now, the mechanism is undocumented. Since calcium is an important second messenger in both immune and glial cells, we studied the effects of glycine on intracellular calcium signaling. We found that millimolar concentrations of glycine enhance microglial intracellular calcium transients induced by 100 μM ATP or by 500 nM thapsigargin. This modulation was unaffected by the glycine receptor antagonist strychnine and could not be mimicked by glycine receptor agonists such as taurine or β-alanine, indicating glycine receptor independency. The modulation of calcium responses could be mimicked by several structurally related amino acids (e.g., serine, alanine, or glutamine) and was inhibited in the presence of the neutral amino acid transporter substrate α-aminoisobutyric acid (AIB). We correlated these findings to immunofluorescence glycine uptake experiments which showed a clear glycine uptake which was inhibited by AIB. Furthermore, all amino acids that were shown to modulate calcium responses also evoked AIB-sensitive inward currents, mainly carried by sodium, as demonstrated by patch clamp experiments. Based on these findings, we propose that sodium-coupled neutral amino acid transporters are responsible for the observed glycine modulation of intracellular calcium responses. |
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Authors:
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Jimmy Van den Eynden; Kristof Notelaers; Bert Brône; Daniel Janssen; Katherine Nelissen; Sheen Sahebali; Inge Smolders; Niels Hellings; Paul Steels; Jean-Michel Rigo |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-25 |
Journal Detail:
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Title: Pflugers Archiv : European journal of physiology Volume: - ISSN: 1432-2013 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Biomedical Research, Hasselt University and Transnationale Universiteit Limburg, Agoralaan, Building C, 3590, Diepenbeek, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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