Zelena Dóra, Makara Gábor B, Nagy György M
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Endocrine. 2003 Jul;21(2):147-52. doi: 10.1385/ENDO:21:2:147.
The aim of the present study was to investigate the role of endogenous excitatory amino acid receptors in suckling- induced prolactin (PRL) elevation. Glutamate is known to be the dominant excitatory neurotransmitter and may act simultaneously on different glutamatergic receptor subtypes. MK-801 (dizocilpine) is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA), while GyKI 52466 is an antagonist of the R,S-alpha-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/ kainate receptor subtypes. Using the combination of the two receptorsubtype antagonists, we tested the hypothesis that parallel blockade of more than one subtype is more effective. Low-dose MK-801 (0.033 mg/kg) had no effect on suckling-induced PRL elevation after 4 h of separation. When injected alone, 10 mg/kg of GyKI 52466 was also ineffective, but in combination with low-dose MK-801 it efficiently diminished the sucklinginduced PRL elevation while lactation proceeded. The same dose of GyKI 52466 combined with 0.2 mg/kg of MK-801 (a combination that in other studies was able to block the foot-shock-induced PRL elevation) was more effective. Simultaneous blockade of the two ionotropic glutamate receptors with 0.2 mg/kg of MK-801 and 10 mg/kg of GyKI 52466 caused a decline in plasma PRL concentration of continuously suckling mothers. We conclude that the endogenous glutamatergic system has an important role in suckling-induced PRL elevation and in the maintenance of constantly high PRL levels in lactating mothers. Furthermore, the NMDA and AMPA/kainate receptor subtypes can interact with each other in this process.
本研究的目的是探讨内源性兴奋性氨基酸受体在哺乳诱导的催乳素（PRL）升高过程中的作用。已知谷氨酸是主要的兴奋性神经递质，可能同时作用于不同的谷氨酸能受体亚型。MK-801（地佐环平）是N-甲基-D-天冬氨酸（NMDA）的非竞争性拮抗剂，而GyKI 52466是R,S-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）/海人藻酸受体亚型的拮抗剂。我们使用这两种受体亚型拮抗剂的组合，来检验同时阻断多个亚型会更有效的假设。低剂量的MK-801（0.033mg/kg）在分离4小时后对哺乳诱导的PRL升高没有影响。单独注射时，10mg/kg的GyKI 52466也无效，但与低剂量的MK-801联合使用时，在哺乳过程中能有效降低哺乳诱导的PRL升高。相同剂量的GyKI 52466与0.2mg/kg的MK-801联合使用（在其他研究中该组合能够阻断足部电击诱导的PRL升高）则更有效。用0.2mg/kg的MK-801和10mg/kg的GyKI 52466同时阻断两种离子型谷氨酸受体，会使持续哺乳的母亲血浆PRL浓度下降。我们得出结论，内源性谷氨酸能系统在哺乳诱导的PRL升高以及维持哺乳期母亲持续高水平的PRL中起重要作用。此外，NMDA和AMPA/海人藻酸受体亚型在此过程中可能相互作用。
