Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavengingnitric oxide

Because ascorbic acid (AA) is concentrated in synaptic vesicles containing glutamic acid, we hypothesized that AA might act as a neurotransmitter. Bec ause AA is an antioxidant, it might therefore inhibit nitric oxidergic (NOe rgic) activation of luteinizing hormone-releasing hormone (LH-RH) release f rom medial basal hypothalamic explants by chemically reducing NO. Cell memb rane depolarization induced by increased potassium concentration [K+] incre ased medium concentrations of both AA and LH-RH. An inhibitor of NO synthas e (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 me diates release of both AA and LH-RH. Calcium-free medium blocked not only t he increase in AA in the medium but also the release of LH-RH. Sodium nitro prusside, which releases NO, stimulated LH-RH release and decreased the con centration of AA in the incubation medium, presumably because the NO releas ed oxidized AA to dehydro-AA. AA (10(-5) to 10(-3) M) had no effect on basa l LH-RH release but completely blocked high [K+]and nitroprusside-induced L H-RH release. N-Methyl-D-aspartic acid (NMDA), which mimics the action of t he 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: stim ulation of LH-RH release by chemically reducing the NO released by the NOer gic neurons.