Neurokinin-1 receptors in the rat nucleus tractus solitarius: Pre- and postsynaptic modulation of glutamate and GABA release
Neurokinin-1 receptors in the rat nucleus tractus solitarius: Pre- and postsynaptic modulation of glutamate and GABA release
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DOI：
10.1016/j.neuroscience.2004.05.025
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Jones, RSG
中科院分区：
文献类型：
--
作者：
Bailey, CP;Maubach, KA;Jones, RSG
神经激动素，如P物质和神经激动素A，一直被认为是孤束核中的神经递质或调节剂。然而，这些多肽的受体的作用和位置仍然不清楚。我们在脑片上用全细胞膜片钳记录研究了神经激肽-1(NK1)受体亚型在大鼠孤束核激活的后果。应用8-Ala-Phe-Phe-Pro-MeLeu-D-Pro[spiro-gamma-lactam]-Leu-Trp-NH2(一种特定的NK1激动剂)或神经激动素A可引起由突触后NK1受体直接激活介导的去极化，明显表现为一种缓慢的内向电流。这种作用在河豚毒素和蛋白激酶C依赖的情况下是保守的，因为它被一种特定的蛋白激酶C抑制剂2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide，阻断。此外，观察到自发兴奋性突触后电流的频率和幅度增加，反映了NK1受体激活引起的谷氨酸释放增加。这种效应被河豚毒素所消除，这表明它是由于NK1受体引起的躯体树突状细胞兴奋后传入神经元放电增加所致。此外，自发抑制性突触后电流的频率和幅度增加，表明NK1受体的激活促进了GABA的释放。然而，NK1受体的激活并未改变微小抑制性突触后电流的幅度，但频率的增加持续存在。这些结果表明，NK1受体位于GABA能神经元的突触前终末和躯体树突部位。GABA释放的增加也被证明是蛋白激酶C依赖的。结果表明，大鼠孤束核内既有兴奋性神经元，也有抑制性神经元。这些受体的激活可以导致GABA和谷氨酸的释放增加，这表明NK1受体在大鼠孤束核中起着至关重要的调节作用。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
Neurokinins such as substance P and neurokinin A have long been thought to act as neurotransmitters or modulators in the nucleus tractus solitarius. However, the role and location of the receptors for these peptides have remained unclear. We examined the consequences of activation of the neurokinin-1 (NK1) receptor subtype in the rat nucleus tractus solitarius using whole-cell patch clamp recordings in brain slices. Application of 8-Ala-Phe-Phe-Pro-MeLeu-D-Pro[spiro-gamma-lactam]-Leu-Trp-NH2 (a specific NK1, agonist) or neurokinin A resulted in depolarization, evident as a slow inward current, mediated by direct postsynaptic NK1, receptor activation. The effect was conserved in the presence of tetrodotoxin, and protein kinase C-dependent since it was blocked by 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide, a specific protein kinase C inhibitor. In addition, an increase in the frequency and amplitude of spontaneous excitatory postsynaptic currents was observed, reflecting increased glutamate release induced by NK1, receptor activation. This effect was abolished by tetrodotoxin, suggesting that it resulted from increased firing in afferent neurons, subsequent to somatodendritic excitation via NK1, receptors. Furthermore, spontaneous inhibitory postsynaptic currents were increased in frequency and amplitude showing that GABA release was promoted by NK1, receptor activation. However, amplitude of miniature inhibitory postsynaptic currents was unaltered by NK1, receptor activation, but the increase in frequency persisted. These findings suggest that NK1, receptors are located on presynaptic terminals as well as at somatodendritic sites of GABAergic neurons. The increase in GABA release was also shown to be protein kinase C-dependent. The data presented here show NK1, receptors in the rat nucleus tractus solitarius are present both excitatory and inhibitory neurons. Activation of these receptors can result in increases in release of both GABA and glutamate, suggesting a crucial modulatory role for NK1, receptors in the rat nucleus tractus solitarius. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.