Document Detail

Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide.
MedLine Citation:
PMID:  10677552     Owner:  NLM     Status:  MEDLINE    
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.
S Karanth; W H Yu; A Walczewska; C Mastronardi; S M McCann
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  2000-03-23     Completed Date:  2000-03-23     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1891-6     Citation Subset:  IM    
Pennington Biomedical Research Center (Louisiana State University), 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
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MeSH Terms
Ascorbic Acid / pharmacology*
Calcium / metabolism
Free Radical Scavengers / metabolism
Gonadotropin-Releasing Hormone / metabolism*
Hypothalamus / drug effects*
Models, Neurological
N-Methylaspartate / pharmacology
Neurotransmitter Agents / pharmacology*
Nitric Oxide / pharmacology*
Nitroprusside / pharmacology
Potassium / pharmacology
Rats, Sprague-Dawley
omega-N-Methylarginine / pharmacology
Grant Support
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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