An excitatory neurotransmitter
NMDA is an agonist of NMDA-receptor [1].
NMDA is a glutamate-like excitatory substance and is a particularly potent excitant. NMDA binds to NMDA-receptor and interacts with it. This interaction causes a conformational change in the receptor or associated membrane molecules, which opened pores to allow extracellular sodium ions to flow down their electrochemical gradient and depolarise the cell. However, NMDA is proved to be a poor substrate for the uptake transporters, suggesting that the excitatory effect could not be an indirect consequence of glutamate uptake. Besides that, NMDA is found to increase intracellular calcium and release arachidonic acid, both of which generate oxygen radicals, subsequently inducing neuronal death [1, 2].
参考文献:
[1] Watkins JC, Jane DE. The glutamate story. Br J Pharmacol. 2006 Jan;147 Suppl 1:S100-8.
[2] Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J. NMDA-dependent superoxide production and neurotoxicity. Nature. 1993 Aug 5;364(6437):535-7.
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Kinase experiment: |
Adrenal membranous homogenate suspensions are incubated with 10 nM [3H]Glu in 500/zl 50 mM Tris-acetate buffer (pH 7.4) at 2°C or 30°C in the presence and absence of various compounds. Incubation is terminated by the addition of 3 mL ice-cold buffer and subsequent filtration through a Whatman GF/B glass filter under a constant vacuum of 15 mm Hg. After washing the filter 4 times with 3 mL icecold buffer, the radioactivity trapped on the filter is measured by a liquid scintillation spectrometer using 5 mL modified Triton-toluene scintillant at a counting efficiency of 40-42%. The radioactivity found in the presence of 1 mM non-radioactive Glu is subtracted from each experimental value to obtain the specific binding of [3H]GIu in accordance with the y-aminobutyric acid (GABA) receptor binding assay system. The kinetic parameters of [3H]GIu binding, Kd and Bma x, are calculated by Scatchard analysis of the specific binding using a personal computer with a programme for non-linear regression analysis developed in our own laboratory. |
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Animal experiment: |
Thirty male rats are paired with different receptive females for a total of three times (once every 3 days) a week prior to the experiment, only the males that ejaculated at least three times during this period are included. After selecting the male rats with normal ejaculatory ability. Saline (100 nL), NMDA (0.20 nmol in 100 nL saline), and AP-5 (10.0 nmol in 100 nL saline) are adminitration into the bilateral PVN of each male rat in random order. After 5 min, the behavioral testing is performed and recorded as described above. Copulatory behaviors occur once a week and the entire experiment lasted 4 weeks. |
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参考文献: [1]. Xia JD, et al. Centrally mediated ejaculatory response via sympathetic outflow in rats: role of N-methyl-D-aspartic acid receptors in paraventricular nucleus. Andrology. 2016 Nov 16. |
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