DEGRADATION OF NAD BY SYNAPTOSOMES AND ITS INHIBITION BY NICOTINAMIDE MONONUCLEOTIDE - IMPLICATIONS FOR THE ROLE OF NAD AS A SYNAPTIC MODULATOR

DEGRADATION OF NAD BY SYNAPTOSOMES AND ITS INHIBITION BY NICOTINAMIDE MONONUCLEOTIDE - IMPLICATIONS FOR THE ROLE OF NAD AS A SYNAPTIC MODULATOR
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DOI:
10.1111/j.1471-4159.1984.tb06085.x
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发表时间:
1984-01-01
影响因子:
4.7
通讯作者:
RICHARDS, CD
RICHARDS, CD
中科院分区:
医学2区
文献类型:
--
作者:
SNELL, CR;SNELL, PH;RICHARDS, CD

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NAD被完整大鼠脑突触体中存在的胞外酶迅速降解。所涉及的酶具有在烟酰胺糖苷键处切割分子的NAD酶的特异性,并且被NMN抑制。这种抑制剂没有取代特异性结合的NAD的大鼠脑细胞膜或影响电活动在豚鼠海马。在结合测定中包括MNM,允许明确证明大鼠脑突触体膜上的2个特异性NAD结合位点(KD 1,82 nM,KD 2,1.98 μ M)。用NMN抑制NAD降解后,NAD对豚鼠海马诱发突触活动的抑制作用不被阻断。这些结果的生理意义的功能NAD作为一种神经递质或神经调质在中枢神经系统进行了讨论。
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.