Somers D L, Beckstead R M
Department of Anatomy and Cell Biology, Medical University of South Carolina, Charleston.
J Pharmacol Exp Ther. 1992 Aug;262(2):823-33.
A reduction of striatal excitatory amino acids or of corticostriatal axons alters substance P (SP) and met5-enkephalin (ME) biosynthesis in striatal neurons of the rat. To determine the role of the N-methyl-D-aspartate (NMDA) receptor in this effect, adult rats were treated acutely with a single i.c.v. injection or chronically by 7 days of continuous infusion of an NMDA antagonist. The striatal content of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA was assessed by in situ hybridization histochemistry while the content of SP and ME in, respectively, the substantia nigra and globus pallidus was measured by quantitative radioimmunocytochemistry. Eight hours after a single injection, striatal PPT and PPE mRNA levels were significantly reduced. At 24 hr, the level of PPE had returned to control level whereas that of PPT mRNA remained depressed. Nigral SP and pallidal ME levels were not acutely changed. Chronically, the effect of NMDA antagonist at low doses was to increase the striatal content of PPE mRNA. However, at higher concentrations, the effect was to reduce in a dose-dependent manner the striatal content of PPT and PPE mRNA and the level of pallidal ME. The nigral level of SP did not change significantly at any dose. The results suggest that excitatory amino acid transmission mediated by the NMDA receptor serves as a tonic signal to stimulate neuroactive peptide biosynthesis.
纹状体兴奋性氨基酸或皮质纹状体轴突的减少会改变大鼠纹状体神经元中P物质（SP）和甲硫氨酸脑啡肽（ME）的生物合成。为了确定N-甲基-D-天冬氨酸（NMDA）受体在此效应中的作用，成年大鼠通过单次脑室内注射进行急性处理，或通过连续7天输注NMDA拮抗剂进行慢性处理。通过原位杂交组织化学评估前速激肽原（PPT）和前脑啡肽原（PPE）mRNA的纹状体含量，同时通过定量放射免疫细胞化学分别测量黑质和苍白球中SP和ME的含量。单次注射8小时后，纹状体PPT和PPE mRNA水平显著降低。24小时时，PPE水平恢复到对照水平，而PPT mRNA水平仍处于抑制状态。黑质SP和苍白球ME水平没有急性变化。长期来看，低剂量NMDA拮抗剂的作用是增加纹状体PPE mRNA的含量。然而，在较高浓度下，其作用是剂量依赖性地降低纹状体PPT和PPE mRNA的含量以及苍白球ME的水平。在任何剂量下，黑质SP水平均无显著变化。结果表明，由NMDA受体介导的兴奋性氨基酸传递作为一种紧张性信号来刺激神经活性肽的生物合成。
