Inhibition by ascorbic acid of NMDA-evoked acetylcholine release in rabbit caudate nucleus

The interaction of ascorbic acid and of dehydroascorbic acid with acetylcholine (ACh) release in rabbit caudate nucleus was investigated. The presence of ascorbic acid in the superfusion medium decreased the release of ACh evoked by N-methyl-D-aspartate (NMDA), but not by electrical stimulation. The pH of the buffer was always maintained at 7.4. Inhibition occurred even at 570 mumol/l ascorbic acid, a concentration which is widely employed in transmitter release experiments. In vivo this concentration may be reached extracellularly in brain tissue. Both ascorbic acid and dehydroascorbic acid inhibited the NMDA-evoked ACh release to the same degree in a non-competitive manner. The nearly identical action of ascorbic acid and dehydroascorbic acid makes a mode of action by lipid peroxidation or by redox phenomena unlikely. The mechanism of action underlying the described effects is unknown.