Details

Autor(en) / Beteiligte

• Karanth, Sharada
• Yu, Wen H.
• Walczewska, Anna
• Mastronardi, Claudio
• McCann, Samuel M.

Titel

Ascorbic Acid Acts as an Inhibitory Transmitter in the Hypothalamus to Inhibit Stimulated Luteinizing Hormone-Releasing Hormone Release by Scavenging Nitric Oxide

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2000-02, Vol.97 (4), p.1891-1896

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

2000

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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), NG-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 (10-5to 10-3M) 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 (10-5to 10-3M) 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.