Neurotensin selectively facilitates glutamatergic transmission in globus pallidus

Neurotensin selectively facilitates glutamatergic transmission in globus pallidus
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DOI:
10.1016/j.neuroscience.2006.05.049
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发表时间:
2006-01-01
期刊:
影响因子:
3.3
通讯作者:
Yung, W. H.
Yung, W. H.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, L.;Yung, K. K. L.;Yung, W. H.

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十三肽神经降压素已被证明可以调节许多大脑区域的神经传递。有证据表明,神经降压素受体存在于苍白球突触前和突触后。全细胞膜片钳记录用于研究神经降压素对大鼠基底神经节核中谷氨酸和 GABA 传输的调节作用。 1 μM 的神经降压素显着增加了谷氨酸受体介导的微型兴奋性突触后电流的频率。相反,神经降压素对 GABA(A) 受体介导的微型抑制性突触后电流没有影响。神经降压素对谷氨酸能传递的突触前促进作用可以通过 C 端片段神经降压素 (8-13) 模拟,但不能通过 N 端片段神经降压素 (1-8) 模拟。选择性神经降压素 1 型受体拮抗剂 SR48692 {2-[(1-(7-氯-4-喹啉基)-5-2(2,6-二甲氧基苯基)吡唑-3-基)羰基氨基]-三环(3.3.1.1.(3.7))-癸-2-羧酸)可阻断神经降压素的这种促进作用,并且其本身对微型兴奋性神经元没有影响。突触后电流。特异性磷脂酶 C 抑制剂 U73122{1-[6-[[17 beta-3-methoyyestra-1,3,5(10)-trien-1 7-yl]amino]hexyl]-1H-pyrrole-2,5-dione) 可显着抑制神经降压素诱导的谷氨酸释放促进。结合报道的苍白球神经降压素突触后去极化,表明神经降压素通过多种机制兴奋苍白球神经元,这可能为进一步研究其参与源自基底神经节的运动障碍提供理论依据。 (c) 2006 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Wholecell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 mu M significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol- 3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid), blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122{1-[6-[[17 beta-3-methoyyestra-1,3,5(10)-trien-1 7-yl]amino]hexyl]-1H-pyrrole-2,5-dione), significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.