Geez, is there anything that ISN'T a neurotransmitter these days? --David Epstein [EMAIL PROTECTED] Sharada Karanth, Wen H. Yu, Anna Walczewska, Claudio Mastronardi, and Samuel M. McCann. Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide. _Proceedings of the National Academy of Sciences_ 97: 1891-1896, Feb 15 2000. ABSTRACT: 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 1 ] increased me-dium 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 concentra-tion of AA in the incubation medium, presumably because the NO released oxidized AA to dehydro-AA. AA (10 25 to 10 23 M) had no effect on basal LH-RH release but completely blocked high [K 1 ]-and nitroprusside-induced LH-RH release. N-Methyl-D-aspartic acid (NMDA), which mimics the action of the excitatory amino acid neu-rotransmitter glutamic acid, releases LH-RH by releasing NO. AA (10 25 to 10 23 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.
