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兴奋性氨基酸受体的非NMDA亚型在猫的面神经后核控制心血管功能中起主要作用。

The non-NMDA subtype of excitatory amino acid receptor plays the major role in control of cardiovascular function by the subretrofacial nucleus in cats.

作者信息

Abrahams T P, Hornby P J, Chen K, Dasilva A M, Gillis R A

机构信息

Department of Pharmacology, Georgetown University, School of Medicine, Washington, D.C.

出版信息

J Pharmacol Exp Ther. 1994 Jul;270(1):424-32.

PMID:7913499
Abstract

Recent studies have reported that microinjection of kynurenic acid (KYN 12.5 nmol), the nonselective Excitatory Amino acid (EAA) antagonist, into the rostral ventrolateral medulla of the cat decreases arterial blood pressure (BP) and inferior cardiac sympathetic nerve discharge. The purpose of our study was to confirm this finding and determine the subtypes of EAA receptor(s) responsible for mediating this effect. This was done by microinjecting various EAA antagonists bilaterally into the SRFN of chloralose-anesthetized animals while monitoring BP and HR. KYN (12.5 nmol; N = 5) produced a decrease in mean BP (31 +/- 9 mmHg, P < .05) with no significant change in HR. To determine the subtype of EAA receptor responsible for eliciting tonic sympathetic outflow from the SRFN, specific antagonists of N-methyl-D-aspartate (NMDA) and non-NMDA EAA receptors were tested. The NMDA receptor antagonist 3-(RS)-Carboxypiperazin-4-yl)-proyl- 1-phosphonic acid (CPP-2.25 nmol; N = 3) microinjected into the SRFN produced a small but significant decrease in BP (-13 +/- 1 mmHg; P < .05). This effect of CPP was significantly less than that seen with KYN. Two antagonists of the non-NMDA subtype of EAA receptor, 6-cyano-7-nitroquinoxaline-2,3-dione (0.05 nmol; N = 4) and gamma-D-glutamylaminomethyl sulphonic acid (2.5 nmol; N = 4), were microinjected into the SRFN. Both of these drugs produced decreases in BP (-29 +/- 4 and -23 +/- 3 mmHg, respectively; P < 0.05) similar to that observed with KYN. No significant changes in HR were noted with CPP, 6 cyano-7-nitroquinoxaline-2,3-dione or gamma-G-glutamylamino-methylsulfonate. These data indicate that a non-NMDA EAA receptor plays the major role in control of cardiovascular function by the SRFN.

摘要

最近的研究报道,向猫的延髓头端腹外侧微注射非选择性兴奋性氨基酸(EAA)拮抗剂犬尿喹啉酸(KYN,12.5 nmol)可降低动脉血压(BP)并减少心脏下交感神经放电。我们研究的目的是证实这一发现,并确定介导此效应的EAA受体亚型。通过在监测血压和心率的同时,向用氯醛糖麻醉的动物的延髓头端腹外侧网状核(SRFN)双侧微注射各种EAA拮抗剂来实现这一目的。KYN(12.5 nmol;N = 5)使平均血压降低(31±9 mmHg,P <.05),而心率无显著变化。为了确定负责引发SRFN紧张性交感神经输出的EAA受体亚型,测试了N-甲基-D-天冬氨酸(NMDA)和非NMDA EAA受体的特异性拮抗剂。向SRFN微注射NMDA受体拮抗剂3-(RS)-羧基哌嗪-4-基)-丙基-1-膦酸(CPP,2.25 nmol;N = 3)可使血压小幅但显著降低(-13±1 mmHg;P <.05)。CPP的这种作用明显小于KYN的作用。将两种非NMDA亚型EAA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮(0.05 nmol;N = 4)和γ-D-谷氨酰胺甲基磺酸(2.5 nmol;N = 4)微注射到SRFN中。这两种药物均使血压降低(分别为-29±4和-23±3 mmHg;P <0.05),与KYN观察到的情况相似。使用CPP、6-氰基-7-硝基喹喔啉-2,3-二酮或γ-G-谷氨酰胺甲基磺酸盐时,心率无显著变化。这些数据表明,非NMDA EAA受体在SRFN对心血管功能的控制中起主要作用。

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