Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide.
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.
Karanth
S
S
Pennington Biomedical Research Center (Louisiana State University), 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
Yu
W H
WH
Walczewska
A
A
Mastronardi
C
C
McCann
S M
SM
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016166:Free Radical Scavengers; D018377:Neurotransmitter Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D001205:Ascorbic Acid; D011188:Potassium; D002118:Calcium