N-甲基-D-天冬氨酸、一氧化氮和血清素在青春期前雄性大鼠催乳素分泌调控中的相互作用。

Aguilar E, Tena-Sempere M, Aguilar R, González D, Pinilla L

Department of Physiology, Faculty of Medicine, University of Córdoba, Spain.

Eur J Endocrinol. 1997 Jul;137(1):99-106. doi: 10.1530/eje.0.1370099.

The role of N-methyl-D-aspartate (NMDA) in the control of prolactin (PRL) secretion was analysed in prepubertal male rats. In experiment 1, males of different ages were decapitated after administration of NMDA or vehicle. In experiment 2, 30-day-old males were killed at different times after administration of vehicle, NMDA, MK-801 (a non-competitive NMDA antagonist) or NMDA plus MK-801. In experiment 3, 23-day-old males were sham-orchidectomized or orchidectomized. Orchidectomized males were or were not implanted with Silastic capsules containing different amounts of testosterone. On day 30, the animals were decapitated after administration of vehicle, NMDA or MK-801. In experiment 4, 30-day-old male rats were decapitated after being injected with vehicle, NMDA, Nw-nitro-L-arginine methyl ester (NAME) (an inhibitor of nitric oxide (NO) synthase), or NMDA plus NAME. Serum PRL concentrations, and dopamine pituitary and hypothalamic content were measured. In experiment 5, males pretreated with vehicle or NAME were killed after administration of the precursor of serotonin synthesis 5-hydroxytryptophan (5-HTP), the 5-HT1 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or the 5-HT2 agonist (+/-) 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Finally, the effects of NMDA, NAME and sodium nitroprusside (SNP) were tested in dispersed adenohypophyseal cells. We found that: (1) antagonism of NMDA receptors with MK-801 decreased PRL secretion in intact, orchidectomized and orchidectomized-testosterone treated male rats; (ii) NMDA inhibited PRL release in vivo through an increase in dopamine release and this effect was potentiated by NAME and prevented by testosterone; (iii) NMDA inhibited PRL, secretion in vitro and this effect was observed in presence of both SNP and NAME; (iv) NAME blocked the stimulatory effects of 5-HTP and DOI on PRL secretion. We conclude that endogenous glutamate stimulates PRL release and that NO might have a pivotal role in the mechanisms involved in the control of PRL release, inhibiting the release of dopamine and modulating the effects of NMDA and 5-HT.

在青春期前雄性大鼠中分析了N-甲基-D-天冬氨酸（NMDA）在催乳素（PRL）分泌控制中的作用。在实验1中，给不同年龄的雄性大鼠注射NMDA或溶剂后断头。在实验2中，给30日龄雄性大鼠注射溶剂、NMDA、MK-801（一种非竞争性NMDA拮抗剂）或NMDA加MK-801后，在不同时间处死。在实验3中，对23日龄雄性大鼠进行假去势或去势。去势雄性大鼠植入或未植入含不同量睾酮的硅橡胶胶囊。在第30天，给动物注射溶剂、NMDA或MK-801后断头。在实验4中，给30日龄雄性大鼠注射溶剂、NMDA、Nω-硝基-L-精氨酸甲酯（NAME）（一种一氧化氮（NO）合酶抑制剂）或NMDA加NAME后断头。测量血清PRL浓度、多巴胺垂体和下丘脑含量。在实验5中，给预先用溶剂或NAME处理的雄性大鼠注射5-羟色胺合成前体5-羟色氨酸（5-HTP）、5-HT1受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）或5-HT2激动剂（±）2,5-二甲氧基-4-碘苯丙胺盐酸盐（DOI）后处死。最后，在分散的腺垂体细胞中测试了NMDA、NAME和硝普钠（SNP）的作用。我们发现：（1）用MK-801拮抗NMDA受体可降低完整、去势和去势-睾酮处理的雄性大鼠的PRL分泌；（ii）NMDA通过增加多巴胺释放来抑制体内PRL释放，这种作用被NAME增强，被睾酮阻止；（iii）NMDA在体外抑制PRL分泌，在SNP和NAME存在时均观察到这种作用；（iv）NAME阻断了5-HTP和DOI对PRL分泌的刺激作用。我们得出结论，内源性谷氨酸刺激PRL释放，并且NO可能在PRL释放控制机制中起关键作用，抑制多巴胺释放并调节NMDA和5-HT的作用。