Characterization and possible opioid modulation of N-methyl-D-aspartic acid induced increases in serum luteinizing hormone levels in the developing male rat.
Characterization and possible opioid modulation of N-methyl-D-aspartic acid induced increases in serum luteinizing hormone levels in the developing male rat.
复制标题
N-甲基-D-天冬氨酸的表征和可能的阿片类药物调节可诱导发育中的雄性大鼠血清黄体生成素水平增加。
DOI：
10.1016/0024-3205(88)90038-0
复制
发表时间：
1988
期刊：
影响因子：
6.1
通讯作者：
Bell,RD
中科院分区：
文献类型：
--
作者：
Cicero,TJ;Meyer,ER;Bell,RD
以前曾报道兴奋性氨基酸N-甲基-D-天冬氨酸（NMDA）可促进年轻雄性大鼠血清促黄体生成素（LH）水平的升高。本研究旨在确定NMDA对LH的影响是否通过下丘脑释放LHRH来介导。我们还研究了NMDA敏感的神经元通路是否与内源性阿片系统相互作用，调节LHRH的释放和NMDA诱发的血清LH增加的个体发生。我们发现，NMDA诱导的LH增加的年龄-反应曲线是倒U型;在早期（10和15天），氨基酸在增加LH水平方面效果甚微，从出生后第20-40天起效果最大，此后迅速失去疗效，因此在成年动物中几乎没有活性。剂量反应曲线显示，成年动物对NMDA的敏感性比年轻动物低10倍以上。我们的研究还表明，NMDA通过直接影响下丘脑释放LHRH来增加LH，因为一种有效的LHRH拮抗剂竞争性抑制NMDA的作用。最后，我们观察到，吗啡竞争性抑制NMDA对LH释放的影响，这表明NMDA敏感的神经元通路和那些内源性阿片类药物的系统，这是已知的调节LH释放之间的关系。
It has been previously reported that the excitatory amino acid, N-methyl-D-aspartic acid (NMDA), elicits prompt increases in serum luteinizing hormone (LH) levels in young male rats. The present studies were carried out to determine whether the effects of NMDA on LH were mediated by the release of LHRH from the hypothalamus. We also examined whether NMDA-sensitive neuronal pathways interacted with the endogenous opioid system regulating LHRH release and the ontogeny of NMDA-evoked increases in serum LH. We found that the age-response curve for NMDA-induced increases in LH was an inverted U; at early ages (10 and 15 days) the amino acid was marginally effective in increasing LH levels, it became maximally effective from post-natal days 20–40 and thereafter rapidly lost its efficacy such that it was virtually inactive in adult animals. Dose-response curves revealed that adult animals were more than 10-fold less sensitive to NMDA than their younger counterparts. Our studies also demonstrated that NMDA increased LH via a direct effect on the hypothalamic release of LHRH since a potent LHRH antagonist competitively inhibited the effects of NMDA. Finally, we observed that morphine competitively inhibited the effects of NMDA on LH release, suggesting a relationship between NMDA-sensitive neuronal pathways and those endogenous opioid-containing systems which are known to regulate LH release.