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大鼠孤束核中代谢型谷氨酸受体的亚型

Subtypes of metabotropic glutamate receptors in the nucleus of the solitary tract of rats.

作者信息

Matsumura K, Tsuchihashi T, Kagiyama S, Abe I, Fujishima M

机构信息

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan.

出版信息

Brain Res. 1999 Sep 25;842(2):461-8. doi: 10.1016/s0006-8993(99)01889-2.

Abstract

We have determined the role of subgroups of metabotropic glutamate receptors (mGluRs) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. Unilateral microinjection of (S)-3, 5-dihydroxyphenylglycine (3,5-DHPG), an agonist of group I mGluRs, into the NTS significantly decreased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (-19. 4+/-2.6 mmHg, -16.4+/-5.1 beats/min, and -30.6+/-5.7% by 1 nmol). Microinjection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 nmol), a putative antagonist of group I mGluRs, into the NTS caused transient decreases in MAP and RSNA, followed by sustained increases in MAP (+8.3+/-2.4 mmHg) and RSNA (+27.7+/-10.8%). Pretreatment with AIDA failed to prevent the cardiovascular and RSNA responses to microinjection of 3,5-DHPG. Unilateral microinjection of (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of group II mGluRs, into the NTS also significantly decreased MAP, HR, and RSNA, whose responses were not inhibited by pre-microinjection of (2S)-alpha-ethylglutamic acid (EGLU; 2 nmol), a putative antagonist of group II mGluRs. On the other hand, unilateral microinjection of L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of group III mGluRs, into the NTS caused dose-related decreases in MAP (-8. 3+/-1.5 mmHg by 0.1 nmol and -45.1+/-3.4 mmHg by 0.3 nmol), HR, and RSNA (-21.3+/-3.9% by 0.1 nmol and -77.2+/-6.5% by 0.3 nmol), whose responses were suppressed by pre-microinjection of (R, S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG; 0.3 nmol), an antagonist of group III mGluRs. These results suggest that all subgroups of mGluRs participate in cardiovascular and sympathetic regulations in the NTS of rats, and that endogenous group I mGluRs in the NTS may contribute to tonic cardiovascular and sympathetic regulations.

摘要

我们已经确定了代谢型谷氨酸受体(mGluRs)亚组在正常血压Wistar大鼠孤束核(NTS)中的作用。向NTS单侧微量注射I组mGluRs激动剂(S)-3,5-二羟基苯甘氨酸(3,5-DHPG)可显著降低平均动脉压(MAP)、心率(HR)和肾交感神经活动(RSNA)(1 nmol时分别降低-19.4±2.6 mmHg、-16.4±5.1次/分钟和-30.6±5.7%)。向NTS单侧微量注射I组mGluRs的假定拮抗剂(R,S)-1-氨基茚满-1,5-二羧酸(AIDA;1 nmol)会导致MAP和RSNA短暂降低,随后MAP(+8.3±2.4 mmHg)和RSNA(+27.7±10.8%)持续升高。用AIDA预处理未能阻止对微量注射3,5-DHPG的心血管和RSNA反应。向NTS单侧微量注射II组mGluRs激动剂(S)-4-羧基-3-羟基苯甘氨酸(4C3HPG)也可显著降低MAP、HR和RSNA,其反应不受II组mGluRs假定拮抗剂(2S)-α-乙基谷氨酸(EGLU;2 nmol)预先微量注射的抑制。另一方面,向NTS单侧微量注射III组mGluRs激动剂L(+)-2-氨基-4-膦酰丁酸(L-AP4)会导致MAP(0.1 nmol时降低-8.3±1.5 mmHg,0.3 nmol时降低-45.1±3.4 mmHg)、HR和RSNA(0.1 nmol时降低-21.3±3.9%,0.3 nmol时降低-77.2±6.5%)呈剂量相关降低,其反应被III组mGluRs拮抗剂(R,S)-α-环丙基-4-膦酰苯甘氨酸(CPPG;0.3 nmol)预先微量注射所抑制。这些结果表明,mGluRs的所有亚组都参与大鼠NTS中的心血管和交感神经调节,并且NTS中的内源性I组mGluRs可能有助于紧张性心血管和交感神经调节。

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