Sivam S P, Krause J E
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Gary 46408.
J Neurochem. 1992 Dec;59(6):2278-84. doi: 10.1111/j.1471-4159.1992.tb10121.x.
The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是检测在对脊髓和基底神经节这两个神经系统进行慢性药理干预后,P物质(SP)及其受体(也称为NK1受体)的合成是否受到协同调节。在一组实验中,在出生后早期(出生后第3天)皮下注射辣椒素,以诱导脊髓传入感觉神经元变性。在另一组实验中,通过两种方法实现多巴胺能传递的中断:(a)在出生后早期使用神经毒素6-羟基多巴胺使多巴胺能神经元去神经支配,(b)在成年动物中使用氟哌啶醇通过受体阻断来阻断多巴胺能传递。通过放射免疫测定法对脊髓、纹状体或两者进行速激肽[SP和神经激肽A(NKA)]和阿片肽[[Met5]-脑啡肽(ME)和强啡肽A(1-8)(DYN)]的定量分析。通过Northern印迹或溶液杂交分析确定脊髓(C5至T1节段)、纹状体或显微解剖的黑质中总SP编码前速激肽(PPT)mRNA和SP受体(SPR)mRNA 的丰度。通过高效液相色谱法对胺及其酸性代谢产物进行定量分析。出生后早期皮下注射辣椒素增加了热板试验中的潜伏期,降低了SP和NKA水平,增加了PPT mRNA水平,并且不影响脊髓中的SPR mRNA水平。脊髓内的SP系统可能试图补偿传入SP输入的损失,而脊髓受体mRNA水平似乎没有改变。(摘要截短至250字)