| Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide. | |
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MedLine Citation:
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PMID: 10677552 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Because ascorbic acid (AA) is concentrated in synaptic vesicles containing glutamic acid, we hypothesized that AA might act as a neurotransmitter. Because AA is an antioxidant, it might therefore inhibit nitric oxidergic (NOergic) activation of luteinizing hormone-releasing hormone (LH-RH) release from medial basal hypothalamic explants by chemically reducing NO. Cell membrane depolarization induced by increased potassium concentration [K(+)] increased medium concentrations of both AA and LH-RH. An inhibitor of NO synthase (NOS), N(G)-monomethyl-l-arginine (NMMA), prevented the increase in medium concentrations of AA and LH-RH induced by high [K(+)], suggesting that NO mediates release of both AA and LH-RH. Calcium-free medium blocked not only the increase in AA in the medium but also the release of LH-RH. Sodium nitroprusside, which releases NO, stimulated LH-RH release and decreased the concentration of AA in the incubation medium, presumably because the NO released oxidized AA to dehydro-AA. AA (10(-5) to 10(-3) M) had no effect on basal LH-RH release but completely blocked high [K(+)]- and nitroprusside-induced LH-RH release. N-Methyl-d-aspartic acid (NMDA), which mimics the action of the excitatory amino acid neurotransmitter glutamic acid, releases LH-RH by releasing NO. AA (10(-5) to 10(-3) M) inhibited the LH-RH-releasing action of NMDA. AA may be an inhibitory neurotransmitter that blocks NOergic stimulation of LH-RH release by chemically reducing the NO released by the NOergic neurons. |
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Authors:
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S Karanth; W H Yu; A Walczewska; C Mastronardi; S M McCann |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 97 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-23 Completed Date: 2000-03-23 Revised Date: 2013-04-17 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1891-6 Citation Subset: IM |
Affiliation:
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Pennington Biomedical Research Center (Louisiana State University), 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ascorbic Acid / pharmacology* Calcium / metabolism Free Radical Scavengers / metabolism Gonadotropin-Releasing Hormone / metabolism* Hypothalamus / drug effects* Male Models, Neurological N-Methylaspartate / pharmacology Neurotransmitter Agents / pharmacology* Nitric Oxide / pharmacology* Nitroprusside / pharmacology Oxidation-Reduction Potassium / pharmacology Rats Rats, Sprague-Dawley omega-N-Methylarginine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MH51853/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radical Scavengers; 0/Neurotransmitter Agents; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 17035-90-4/omega-N-Methylarginine; 33515-09-2/Gonadotropin-Releasing Hormone; 50-81-7/Ascorbic Acid; 6384-92-5/N-Methylaspartate; 7440-09-7/Potassium; 7440-70-2/Calcium |
| Comments/Corrections | |
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