Cardiovascular response to group I metabotropic glutamate receptor activation in NTS
Cardiovascular response to group I metabotropic glutamate receptor activation in NTS
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DOI：
10.1152/ajpregu.1999.276.5.r1469
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发表时间：
1999-05-01
影响因子：
2.8
通讯作者：
Hasser, EM
中科院分区：
文献类型：
--
作者：
Foley, CM;Vogl, HW;Hasser, EM
谷氨酸被认为是孤束核水平上压力感受性传入的神经递质。孤束核中的外源性谷氨酸通过亲离子型和亲代谢型谷氨酸受体（mGluRs）激活神经元。本研究测试的假设，组I mGluRs在NTS产生降压，心动过缓，和交感神经抑制反应。在麻醉大鼠，单侧30-nl微量注射组I-选择性mGluR激动剂3，5-二羟基苯甘氨酸（DHPG）到NTS降低平均动脉压，心率，腰交感神经活动。产生50%最大反应（ED 50）的药物剂量为50-100 μ M。对微量注射等浓度的DHPG或一般mGluR激动剂1-氨基环戊烷-1S，3R-二羧酸（ACPD）的反应产生类似的心血管效应。用α-甲基-4-羧基苯甘氨酸（MCPG）阻断NTS对mGluRs的作用，可消除注射DHPG或ACPD的心血管反应。用犬尿烯酸阻断离子型谷氨酸受体并没有减弱对DHPG或ACPD注射的反应。这些数据表明，DHPG和ACPD激活NTS中的mGluRs，不需要离子型谷氨酸受体来产生心血管反应。在NTS中，I组mGluRs产生与参与减少交感神经流出、心率和动脉压的神经元的兴奋一致的反应。
Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus tractus solitarius (NTS). Exogenous glutamate in the NTS activates neurons through ionotropic and metabotropic glutamate receptors (mGluRs). This study tested the hypothesis that group I mGluRs in the NTS produce depressor, bradycardic, and sympathoinhibitory responses. In urethan-anesthetized rats, unilateral 30-nl microinjections of the group I-selective mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The dose of drug that produced 50% of the maximal response (ED50) was 50-100 mu M. The response to microinjection of equal concentrations of DHPG or the general mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) produced similar cardiovascular effects. The cardiovascular response to injection of DHPG or ACPD was abolished by NTS blockade of mGluRs with alpha-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid did not attenuate the response to DHPG or ACPD injection. These data suggest that DHPG and ACPD activate mGluRs in the NTS and do not require ionotropic glutamate receptors to produce their cardiovascular response. In the NTS the group I mGluRs produce responses that are consistent with excitation of neurons involved in reducing sympathetic outflow, heart rate, and arterial pressure.