Degradation of NAD by Synaptosomes and Its Inhibition by Nicotinamide Mononucleotide: Implications for the Role of NAD as a Synaptic Modulator

Abstract

NAD was rapidly degraded by extracellular enzymes present of intact rat brain synaptosomes. The enzymes involved had the specificity of an NADase cleaving the molecule at the nicotinamide-glycoside linkage and was inhibited by NMN. This inhibitor did not displace specific binding of NAD to rat brain membranes or affect electrical activity in the guinea pig hippocampus. Inclusion of MNM in binding assays allowing unambiguous demonstration of 2 specific NAD binding sites on rat brain synaptosomal membranes (KD1, 82 nM, KD2, 1.98 .mu.M). The depressant action of NAD on the evoked synaptic activity of the guinea pig hippocampus was not blocked after inhibition of NAD degradation with NMN. The physiological implications of these results for the function of NAD as a neurotransmitter or neuromodulator in the CNS are discussed.