NICOTINAMIDE ADENINE DINUCLEOTIDES MIMIC ADENOSINE INHIBITION ON SYNAPTIC TRANSMISSION BY DECREASING GLUTAMATE RELEASE IN RAT HIPPOCAMPAL SLICES

To assess the possible inhibitory action of nicotinamide adenine dinuc leotides on the synaptic release of glutamate, electrophysiological an d biochemical experiments were performed on rat hippocampal slices. Pe rfusion of adenosine, 8-nicotinamide adenine dinucleotide (NAD) or bet a-nicotinamide adenine dinucleotide phosphate (NADP), reversibly inhib ited the field excitatory postsynaptic potentials (fEPSP). Dose-respon se curves for their inhibitory action showed that these three substanc es had a similar potency in the range of concentrations from 0.1 muM t o 100 muM. NADP and adenosine (100 muM) halved the K+-induced release of endogenous glutamate and aspartate, leaving gamma-amino-butyric aci d (GABA) levels unchanged. 3-Isobutyl-1-methylxanthine (IBMX) 200 muM, an antagonist of the P1-purinoreceptors, antagonized the depressant e ffects of these coenzymes on both fEPSP and also on amino acid release . Based on these results we propose that nicotinamide adenine dinucleo tides, similar to adenosine, inhibit excitatory synaptic transmission in the rat hippocampus by decreasing glutamate release from synaptic t erminals.