Reid M S, Hökfelt T, Herrera-Marschitz M, Håkanson R, Feng D M, Folkers K, Goldstein M, Ungerstedt U
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Brain Res. 1990 Nov 5;532(1-2):175-81. doi: 10.1016/0006-8993(90)91757-8.
The effects of intranigral injections of Spantide II, a novel tachykinin antagonist, on extracellular dopamine, and dihydroxyphenylacetic acid (DOPAC) levels in the rat striatum were studied using in vivo microdialysis. The ability of Spantide II to inhibit intranigral substance P or neurokinin A stimulation of striatal dopamine levels was also studied. A unilateral injection (all substances were injected in a volume of 0.2 microliter) of Spantide II (0.7 nmol) into the substantia nigra, pars reticulata (SNR) of halothane anaesthetized rats produced a short-lasting decrease in dopamine levels in the ipsilateral striatum. Striatal DOPAC levels showed no change after Spantide II. A unilateral injection of substance P (0.07 nmol) into the SNR produced an increase in ipsilateral striatal dopamine levels, which was prevented when substance P was co-administered with Spantide II (0.7 nmol). A unilateral injection of neurokinin A (0.09 nmol) into the SNR produced an increase in ipsilateral striatal dopamine levels, which was not modified when neurokinin A was co-administered with Spantide II (0.7 nmol). Immunohistochemical analysis using antisera to tyrosine hydroxylase and neuropeptide K, as well as Cresyl violet staining, revealed that intranigral injections of Spantide II (0.7 nmol) did not produce significant damage in the substantia nigra. The results indicate that Spantide II is not 'neurotoxic' when injected intranigrally, and that it is a selective antagonist of substance P in the substantia nigra. Furthermore, the reduction of striatal dopamine levels after intranigral Spantide II injections suggests that the nigrostriatal dopamine projection is tonically stimulated by striatonigral substance P.
利用体内微透析技术，研究了新型速激肽拮抗剂Spantide II经黑质内注射后对大鼠纹状体细胞外多巴胺及二羟基苯乙酸（DOPAC）水平的影响。还研究了Spantide II抑制黑质内P物质或神经激肽A对纹状体多巴胺水平刺激的能力。向氟烷麻醉大鼠的黑质网状部（SNR）单侧注射（所有物质均以0.2微升的体积注射）0.7纳摩尔的Spantide II，导致同侧纹状体中多巴胺水平出现短暂下降。注射Spantide II后，纹状体DOPAC水平未发生变化。向SNR单侧注射0.07纳摩尔的P物质，可使同侧纹状体多巴胺水平升高，而当P物质与0.7纳摩尔的Spantide II共同给药时，这种升高被阻止。向SNR单侧注射0.09纳摩尔的神经激肽A，可使同侧纹状体多巴胺水平升高，而当神经激肽A与0.7纳摩尔的Spantide II共同给药时，这种升高未被改变。使用抗酪氨酸羟化酶和神经肽K的抗血清进行免疫组织化学分析以及甲酚紫染色显示，向黑质内注射0.7纳摩尔的Spantide II不会对黑质造成明显损伤。结果表明，Spantide II经黑质内注射时无“神经毒性”，且它是黑质中P物质的选择性拮抗剂。此外，黑质内注射Spantide II后纹状体多巴胺水平降低表明，黑质纹状体多巴胺投射受到纹状体黑质P物质的紧张性刺激。
