Authors: Copeland CS, Neale SA, Salt TE

Journal: Neuropharmacology

Publication Date: March 2013

Volume: 66

Pages: 133-142

DOI: 10.1016/j.neuropharm.2012.03.009

Abstract:

The study investigates the role of xanthurenic acid (XA), derived from tryptophan metabolism, as an endogenous Group II metabotropic glutamate receptor (mGlu2 and mGlu3) ligand. The focus is on XA's effects on sensory transmission in the thalamus. Using extracellular single-neuron recordings in the rat ventrobasal thalamus and various administration methods of XA, the researchers found that XA modulates sensory inhibition similarly to other Group II mGlu receptor agonists. The study suggests XA as a potential endogenous allosteric agonist for mGlu receptors, highlighting its significance in the pathophysiology of schizophrenia and potential in antipsychotic research.

摘要：

这项研究探讨了黄嘌呤酸（XA），一种来源于色氨酸代谢的分子，作为内源性第二类代谢型谷氨酸受体（mGlu2和mGlu3）配体的作用。研究集中在XA对丘脑感官传递的影响。通过在大鼠腹基底丘脑中的细胞外单神经元记录及各种XA的给药方法，研究发现XA调节感官抑制的作用类似于其他第二类mGlu受体激动剂。研究提出XA作为mGlu受体潜在的内源性变构激动剂的重要性，强调了其在精神分裂症病理生理学中的意义及其在抗精神病药物研究中的潜力。

Key Findings:

1. Sensory Inhibition: XA reduces sensory inhibition in the thalamus, comparable to other Group II mGlu receptor agonists.
2. Neurotransmission Modulation: XA affects neurotransmission through its action on Group II mGlu receptors.
3. Potential Endocoid: XA may be the first endogenous allosteric agonist for mGlu receptors, termed ‘endocoid’.
4. Schizophrenia Research: The involvement of XA in the kynurenine pathway and Group II receptors suggests its potential in antipsychotic drug research.

主要发现：

1. 感官抑制: XA在丘脑中减少感官抑制，类似于其他第二类mGlu受体激动剂。
2. 神经传递调节: XA通过其对第二类mGlu受体的作用影响神经传递。
3. 潜在内源性变构激动剂: XA可能是第一种mGlu受体的内源性变构激动剂，被称为“endocoid”。
4. 精神分裂症研究: XA在犬尿氨酸途径和第二类受体中的作用表明其在抗精神病药物研究中的潜力。

Methodology:

• Extracellular Single-Neurone Recordings: Conducted in the rat ventrobasal thalamus.
• Iontophoresis and Intravenous Injection: XA was applied both iontophoretically and intravenously.
• Agonists and Antagonists: Various mGlu receptor agonists, antagonists, and positive allosteric modulators were used to investigate XA's effects.

方法学：

· 细胞外单神经元记录: 在大鼠腹基底丘脑中进行。

· 电泳法和静脉注射: XA通过电泳法和静脉注射应用。

· 激动剂和拮抗剂: 使用各种mGlu受体激动剂、拮抗剂和正变构调节剂研究XA的作用。

相关CAS号：

·  Xanthurenic Acid: 59-00-7

·  3-Hydroxykynurenine: 484-78-6

·  Tryptophan: 73-22-3