DL-2-amino-5-phosphonopentanoic acid, a specific N-methyl-D-aspartic acid receptor antagonist, suppresses pulsatile LH release in the rat.
DL-2-amino-5-phosphonopentanoic acid, a specific N-methyl-D-aspartic acid receptor antagonist, suppresses pulsatile LH release in the rat.
复制标题
DL-2-氨基-5-膦酰戊酸是一种特异性 N-甲基-D-天冬氨酸受体拮抗剂，可抑制大鼠脉动性 LH 释放。
DOI：
10.1159/000124951
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发表时间：
1988
影响因子：
4.1
通讯作者：
Plant,TM
中科院分区：
文献类型：
--
作者：
Arslan,M;Pohl,CR;Plant,TM
为了确定神经兴奋性氨基酸是否在产生间歇性下丘脑 GnRH 释放中发挥作用，在雄性大鼠中检查了 N-甲基-D-天冬氨酸 (NMDA) 受体阻断对脉动性 LH 分泌的影响。 NMDA 受体拮抗剂 DL-2-氨基-5-膦基戊酸 (AP5) 在外周给予 NMDA 后抑制下丘脑-垂体促性腺激素轴激活的能力首次在完整大鼠中建立。随后，带有静脉导管的急性去势大鼠（n = 12）以 15 分钟的间隔接受四次连续静脉注射 AP5（3.75 mg/注射/大鼠；约 13.6 mg/kg BW/注射）。在开始 AP5 治疗前 1 小时和开始后 2 小时，每隔 10 分钟采集一次血样，并通过 RI A 测定血浆 LH 浓度。出于对照目的，将正缬氨酸（一种与 AP5 结构相关的氨基酸）以与 NMDA 受体拮抗剂等摩尔的量（2.25 mg/注射/大鼠；约 8.2 mg/kg BW/注射）给予第二组动物（n = 7）。第三组动物（n = 8）仅接受盐水，这是用于注射 AP5 和正缬氨酸的载体。 AP5（而非正缬氨酸）会显着抑制脉动 LH 分泌。这些发现表明，作用于 NMDA 受体的神经兴奋性氨基酸可能在产生下丘脑 GnRH 释放的间歇模式中发挥生理作用。
To determine whether neuroexcitatory amino acids may play a role in generating intermittent hypothalamic GnRH release, the effect of N-methyl-D-aspartate (NMDA) receptor blockade on pulsatile LH secretion was examined in male rats. The ability of the NMDA receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5), to inhibit activation of the hypothalamic-pituitary gonadotroph axis that follows peripheral administration of NMDA, was first established in intact rats. Subsequently, acutely castrated rats (n = 12) bearing venous catheters received four consecutive intravenous injections of AP5 (3.75 mg/injection/rat; approx. 13.6 mg/kg BW/injection) at 15-min intervals. Blood samples were collected at 10-min intervals for 1 h before and 2 h after initiation of AP5 treatment, and plasma LH concentrations were determined by RI A. For control purposes, norvaline, an amino acid structurally related to AP5, was administered to a second group of animals (n = 7) in a quantity (2.25 mg/injection/rat; approx. 8.2 mg/kg BW/injection) equimolar to that of the NMDA receptor antagonist. A third group of animals (n = 8) received only saline, the vehicle employed to inject AP5 and norvaline. AP5, but not norvaline, resulted in a marked suppression of pulsatile LH secretion. These findings suggest that neuroexcitatory amino acids acting at the NMDA receptor may play a physiological role in generating the intermittent mode of hypothalamic GnRH release.