Inhibition of rho-kinase in the nucleus tractus solitarius enhances glutamate sensitivity in rats.
Inhibition of rho-kinase in the nucleus tractus solitarius enhances glutamate sensitivity in rats.
复制标题
抑制孤束核中的 rho 激酶可增强大鼠的谷氨酸敏感性。
作者：
Koji Ito;Y. Hirooka;N. Hori;Yoshikuni Kimura;Yoji Sagara;H. Shimokawa;A. Takeshita;K. Sunagawa
中枢神经系统中的Rho/Rho激酶通路参与树突棘的维持，树突棘形成兴奋性突触的突触后接触位点。神经元中Rho激酶通路的抑制促进树突棘或分支。相反，Rho/Rho激酶途径的激活减少树突棘或分支。最近的研究表明，树突棘的形态变化发生迅速，棘的形态与谷氨酸敏感性。本研究的目的是确定Rho激酶活性是否影响Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）孤束核（NTS）的谷氨酸敏感性。我们首先研究了孤束核单侧谷氨酸注射的影响。SHR的动脉压下降幅度明显小于WKY。然后，我们研究了预注射Y-27632（一种特异性Rho激酶抑制剂）后，单侧谷氨酸注入NTS引起的降压反应。预注射Y-27632增强了两种菌株的谷氨酸反应。然而，增加的幅度显着大于SHR比WKY。此外，我们记录了单个单位活动的NTS神经元从延髓脑片制备。将N-甲基-D-天冬氨酸（NMDA）或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）离子导入记录的神经元，并记录Y-27632灌注前后的神经元活动。Y-27632灌注增加对NMDA和AMPA的反应。这些结果表明，抑制NTS的Rho激酶活性增强WKY和SHR的谷氨酸敏感性，并可能改善SHR受损的谷氨酸敏感性。
The Rho/Rho-kinase pathway in the central nervous system is involved in the maintenance of dendritic spines, which form the postsynaptic contact sites of excitatory synapses. Inhibition of the Rho-kinase pathway in neuron promotes dendritic spines or branches. In contrast, activation of the Rho/Rho-kinase pathway reduces dendritic spines or branches. Recent studies suggest that morphological changes of dendritic spines occur rapidly, and spine morphology is associated with glutamate sensitivity. The aim of the present study was to determine whether Rho-kinase activity affects glutamate sensitivity in the nucleus tractus solitarii (NTS) of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). We first examined the effects of unilateral glutamate injection in the NTS. There was a significantly smaller decrease in arterial pressure in SHR than in WKY. We then examined the depressor responses evoked by unilateral glutamate injection into the NTS after preinjection of Y-27632, a specific Rho-kinase inhibitor. Preinjection of Y-27632 enhanced the glutamate response in both strains. However, the magnitude of the augmentation was significantly greater in SHR than in WKY. Furthermore, we recorded single-unit activity of NTS neurons from medulla brain slice preparations. N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was applied iontophoretically to the recorded neurons, and neuronal activity was recorded before and after Y-27632 perfusion. Y-27632 perfusion increased the response to NMDA and AMPA. These results suggest that inhibition of Rho-kinase activity in the NTS enhances glutamate sensitivity in WKY and SHR and might improve impaired glutamate sensitivity in SHR.
DOI：
10.1152/ajpregu.1998.275.5.r1611
发表时间：
1998-11-01
影响因子：
2.8
作者：
Matsumura, K;Averill, DB;Ferrario, CM
通讯作者：
Ferrario, CM
微量注射到 SHR 孤束核中的谷氨酸和乙酰胆碱改变了心血管反应。
DOI：
10.3109/10641969109042069
发表时间：
1991
期刊：
Clinical and experimental hypertension. Part A, Theory and practice
影响因子：
--
作者：
Talman,WT;Lewis,SJ
通讯作者：
Lewis,SJ