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N-甲基-D-天冬氨酸(NMDA)受体在下丘脑对催乳素分泌的调控中作用的研究。

Studies of the role of the N-methyl-D-aspartate (NMDA) receptor in the hypothalamic control of prolactin secretion.

作者信息

Arslan M, Pohl C R, Smith M S, Plant T M

机构信息

Department of Physiology, University of Pittsburgh School of Medicine, PA 15261.

出版信息

Life Sci. 1992;50(4):295-300. doi: 10.1016/0024-3205(92)90337-o.

DOI:10.1016/0024-3205(92)90337-o
PMID:1531081
Abstract

To further examine the role of excitatory amino acids in the control of prolactin (PRL) secretion, the effects of administering a specific agonist and an antagonist of the N-methyl-D-aspartate (NMDA) receptor on plasma PRL concentrations were examined in the adult male rat. Animals of the Sprague-Dawley strain weighing 250-300 g were implanted with an indwelling cardiac catheter via the right jugular vein. Blood samples were collected through the catheter at 5 min intervals for 40 min, beginning 5 min before the iv administration of drug or the saline vehicle (V). Plasma PRL and luteinizing hormone (LH) concentrations were estimated using RIAs. Groups of animals (n = 5-7) received N-methyl-D,L-aspartate (NMA), D,L-2-amino-5-phosphonopentanoic acid (AP5), AP5 and NMA, norvaline (NOR), or V. The effects of administering the NMDA receptor antagonist alone were studied on two separate occasions. Injection of NMA (4.5 mg/rat) resulted in unambiguous PRL and LH discharges. Treatment with AP5 (9 mg/rat) 1 min prior to NMA administration completely blocked the LH releasing action of NMA, but did not significantly alter the discharge of PRL. Injection of AP5, alone, generally elicited a distinct and robust discharge of PRL, although plasma LH levels in these animals remained unchanged. NOR, an amino acid structurally related to AP5, administered at a dose (5.3 mg/animal) isomolar to that of AP5, was without effect on PRL and LH secretion, as was injection of V alone. These findings suggest that neuroexcitatory amino acids acting at the NMDA receptor may play a role in modulating the activity of neuronal systems that govern the release of both PRL releasing factor (PRF) and PRL inhibiting factor (PIF) into hypophysial portal blood.

摘要

为了进一步研究兴奋性氨基酸在催乳素(PRL)分泌调控中的作用,我们检测了给成年雄性大鼠注射N-甲基-D-天冬氨酸(NMDA)受体的特异性激动剂和拮抗剂对血浆PRL浓度的影响。体重250 - 300 g的Sprague-Dawley品系大鼠通过右颈静脉植入一根留置的心导管。在静脉注射药物或生理盐水载体(V)前5分钟开始,每隔5分钟通过导管采集血样,共采集40分钟。使用放射免疫分析法测定血浆PRL和促黄体生成素(LH)浓度。动物分组(n = 5 - 7)后分别接受N-甲基-D,L-天冬氨酸(NMA)、D,L-2-氨基-5-膦酰基戊酸(AP5)、AP5和NMA、正缬氨酸(NOR)或V。单独给予NMDA受体拮抗剂的效果在两个不同的实验中进行了研究。注射NMA(4.5 mg/大鼠)导致PRL和LH明显释放。在注射NMA前1分钟用AP5(9 mg/大鼠)处理完全阻断了NMA的LH释放作用,但未显著改变PRL的释放。单独注射AP5通常会引起PRL明显且强烈的释放,尽管这些动物的血浆LH水平保持不变。与AP5结构相关的氨基酸NOR,以与AP5等摩尔的剂量(5.3 mg/动物)给药,对PRL和LH分泌没有影响,单独注射V也是如此。这些发现表明,作用于NMDA受体的神经兴奋性氨基酸可能在调节控制PRL释放因子(PRF)和PRL抑制因子(PIF)释放到垂体门脉血中的神经元系统的活性中发挥作用。

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Life Sci. 1992;50(4):295-300. doi: 10.1016/0024-3205(92)90337-o.
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