グルタミン酸作動性ニューロン・マーカー


非必須アミノ酸の一つであるグルタミン酸は、中枢神経系(CNS)で最も重要な興奮性神経伝達物質です。脳内のシナプスのうち半数以上がグルタミン酸を分泌しており、興奮性ニューロンとして働く細胞の中では最も数が多いのはグルタミン酸作動性ニューロンです。

グルタミン酸受容体にはイオンチャネル型と代謝型があります。イオンチャネル型グルタミン酸受容体は神経伝達因子の結合により活性化し、G タンパク質共役受容体(GPCR)である代謝型グルタミン酸受容体は G タンパク質を通してシグナル伝達を行います。

過剰なグルタミン酸濃度により、神経細胞が長期に興奮してイオンが大量に流入すると、神経細胞に毒性をもたらします。脳卒中や中枢神経系の傷害における神経細胞死の主要な原因は、こうしたグルタミン酸の毒性によるものです。

グルタミン酸作動性ニューロンの主なマーカー・タンパク質を紹介します。


vGluT1
A glutamate transporter that transports cytoplasmic glutamate into vesicles.

Zebrafish retina sections stained with anti-vGluT1 (green) (ab77822).

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vGluT2
A glutamate transporter that transports cytoplasmic glutamate into vesicles.

Mouse brain tissue sections stained with anti-vGluT2 (ab79157).

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NMDAR1
An essential subunit of all NMDA receptors.

Rat cortex stained with anti-NMDAR1 (ab17345).

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NMDAR1 modulators

ProductActivity
(+)-MK 801 maleate (Dizocilpine) (ab120027)

Non-competitive NMDAR1 antagonist.  ion channel.

Memantine hydrochloride (ab120249)

NMDAR1 antagonist.

Eliprodil (ab145971)

Non-competitive specific inhibitor of NMDAR1 and/or NMDAR2B subunits.


NMDAR2B
Another NMDA receptor subunit. This subunit forms the glutamate binding site on the NMDA receptors.

Mouse cerebral cortex sections stained with anti-NMDAR2B (ab65783).

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NMDAR2B modulators

ProductActivity
NGHVYEKLSSIE (Interfering peptide) (ab120380)

Peptide (agonist) that competes with clathrin adaptor protein (AP-2) binding to NR2B.

Eliprodil (ab145971)

Non-competitive specific inhibitor of NMDAR1 and/or NMDAR2B subunits.

Gentiopicrin(ab143623)

Downregulates GluN2B-containing NMDA receptors in the NAc.

Ro 25-6981 maleate salt (ab120290)

Potent, highly selective, activity-dependent inhibitor of NMDA receptors that contain the NR2B subunit.

Ifenprodil hemitartrate (ab120111)​

Non-competitive NMDAR2B antagonist acting at the polyamine site.


Glutaminase
An enzyme catalyzing the deamination of glutamine into glutamate.

Human cerebral cortex tissue labeled with anti-glutaminase (ab156876).

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Glutamine synthetase
An enzyme catalyzing the ATP-dependent amidation of glutamate to form glutamine. It is primarily expressed in astrocytes but expression levels rise in neurons in neurodenegerative diseases. When staining for glutamine synthetase, we recommend parallel use of NeuN.

Zebrafish retina sections stained with anti-glutamine synthetase (purple) (ab93439).

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参考文献

  • Baude, A., Strube, C., Tell, F. & Kessler, J.-P. Glutamatergic neurotransmission in the nucleus tractus solitarii: structural and functional characteristics. J. Chem. Neuroanat. 38, 145–53 (2009).
  • Bhatt, J. M., Prakash, A., Suryavanshi, P. S. & Dravid, S. M. Effect of ifenprodil on GluN1/GluN2B N-methyl-D-aspartate receptor gating. Mol. Pharmacol. 83, 9–21 (2013).
  • Fernandes, S. P., Dringen, R., Lawen, A. & Robinson, S. R. Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes. J. Neurochem. 114, 1527–36 (2010).
  • Fischer, G. et al. Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J. Pharmacol. Exp. Ther. 283, 1285–92 (1997).
  • Kotlinska, J. & Liljequist, S. Oral administration of glycine and polyamine receptor antagonists blocks ethanol withdrawal seizures. Psychopharmacology (Berl). 127, 238–244 (1996).
  • Kovacic, P. & Somanathan, R. Clinical physiology and mechanism of dizocilpine (MK-801): electron transfer, radicals, redox metabolites and bioactivity. Oxid. Med. Cell. Longev. 3, 13–22
  • Liu, S.-B. et al. Gentiopicroside attenuates morphine rewarding effect through downregulation of GluN2B receptors in nucleus accumbens. CNS Neurosci. Ther. 18, 652–8 (2012).
  • North, W. G., Gao, G., Jensen, A., Memoli, V. A. & Du, J. NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment. Clin. Pharmacol. 2, 31–40 (2010).
  • Prybylowski, K. et al. The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron 47, 845–57 (2005).
  • Wang, T. & Miller, K. E. Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall. Neuroscience 329, 134–150 (2016).
  • Wyss-Coray, T. et al. Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice. Proc. Natl. Acad. Sci. U. S. A. 99, 10837–10842 (2002).



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