Do K Q, Benz B, Binns K E, Eaton S A, Salt T E
Center for Research in Psychiatric Neuroscience, Department of Psychiatry, University of Lausanne, Route de Cery, CH-1008 Prilly-Lausanne, Switzerland.
Neuroscience. 2004;124(2):387-93. doi: 10.1016/j.neuroscience.2003.08.068.
The sulphur-containing amino acid homocysteic acid (HCA) is present in and released in vitro from nervous tissue and is a potent neuronal excitant, predominantly activating N-methyl-d-aspartate (NMDA) receptors. However, HCA is localised not in neurones but in glial cells [Eur J Neurosci 3 (1991) 1370], and we have shown that it is released from astrocytes in culture upon glutamate receptor activation [Neuroscience 124 (2004) 377]. We now report the in vivo release of HCA from ventrobasal (VB) thalamus following natural stimulation of somatosensory afferents arising from the facial vibrissae of the rat. Simultaneously with multi-unit recording, [35S]-methionine, a HCA precursor, was perfused through a push-pull cannula in VB thalamus of anaesthetized rats. Perfusates were collected before, during and after 4 min stimulation of the vibrissal afferents with an air jet. A marked release of radiolabeled HCA was observed during and after the stimulation. Furthermore, the beta-adrenoreceptor agonist isoproterenol, which is known to evoke HCA release from glia in vitro, was found to increase the efflux of HCA in the perfusate in vivo. In separate experiments, the excitatory actions of iontophoretically applied HCA on VB neurones were inhibited by the NMDA receptor antagonist CPP, but not by the non-NMDA antagonist CNQX. These results suggest a possible "gliotransmitter" role for HCA in VB thalamus. The release of HCA from glia might exert a direct response or modulate responses to other neurotransmitters in postsynaptic neurons, thus enhancing excitatory processes.
含硫氨基酸高半胱氨酸（HCA）存在于神经组织中，并可在体外从神经组织中释放出来，它是一种强效的神经元兴奋剂，主要激活N-甲基-D-天冬氨酸（NMDA）受体。然而，HCA并非定位于神经元，而是存在于神经胶质细胞中[《欧洲神经科学杂志》3（1991）1370]，并且我们已经表明，在培养的星形胶质细胞中，谷氨酸受体激活后HCA会被释放出来[《神经科学》124（2004）377]。我们现在报告，在对大鼠面部触须产生的体感传入神经进行自然刺激后，腹侧基底（VB）丘脑体内HCA的释放情况。在进行多单位记录的同时，将HCA前体[35S]-甲硫氨酸通过推挽式套管灌注到麻醉大鼠的VB丘脑中。在用喷气刺激触须传入神经4分钟之前、期间和之后收集灌注液。在刺激期间和之后观察到放射性标记的HCA有明显释放。此外，已知能在体外诱发神经胶质细胞释放HCA的β-肾上腺素能受体激动剂异丙肾上腺素，被发现能增加体内灌注液中HCA的流出量。在单独的实验中，离子导入法施加的HCA对VB神经元的兴奋作用被NMDA受体拮抗剂CPP抑制，但未被非NMDA拮抗剂CNQX抑制。这些结果表明HCA在VB丘脑中可能具有“神经胶质递质”的作用。神经胶质细胞释放HCA可能会产生直接反应或调节突触后神经元对其他神经递质的反应，从而增强兴奋过程。
