Antonelli T, Tomasini M C, Fuxe K, Agnati L F, Tanganelli S, Ferraro L
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy.
J Neural Transm (Vienna). 2007 Jan;114(1):105-13. doi: 10.1007/s00702-006-0558-7. Epub 2006 Sep 19.
Using mono and dualprobe(s) microdialysis in the basal ganglia of the freely moving rat evidence has been obtained that neurotensin (NT) in threshold concentrations can counteract the D(2) agonist (intrastriatally perfused) induced inhibition of striatal dopamine (DA) release and of pallidal GABA release from the striato-pallidal GABA pathway, effects that are blocked by a NTR(1) antagonist SR48692. These results indicate the existence of antagonistic intramembrane NTR/D(2) receptor interactions in the striatal DA terminals and in the somato-dendritic regions of the striato-pallidal GABA neurons. By the NT-induced reduction of the D(2) mediated signals at the striatal pre- and postjunctional level DA transmission is switched towards a D(1) mediated transmission leading to increased activity in the striatopallidal and striatonigral GABA pathways. The former action will contribute to the motor inhibition and catalepsy found with NT treatment and underlies the use of NT receptor antagonists as a treatment strategy for Parkinson's disease. Nigral NT by an antagonistic NTR/D(2) receptor interaction in the DA cell body and dendrites may also increase nigral DA release leading to a D(2) mediated inhibition of the nigrothalamic GABA pathway. Such an effect, will instead result in antiparkinsonian actions. Thus, increases in NT transmission will have different consequences for the motor system depending upon where in the basal ganglia the increase takes place.
在自由活动大鼠的基底神经节中使用单探针和双探针微透析技术，已获得证据表明，阈浓度的神经降压素（NT）可抵消D（2）激动剂（纹状体内灌注）诱导的纹状体多巴胺（DA）释放抑制以及纹状体-苍白球GABA通路中苍白球GABA释放的抑制，这些作用可被NTR（1）拮抗剂SR48692阻断。这些结果表明，在纹状体DA终末以及纹状体-苍白球GABA神经元的体树突区域存在拮抗的膜内NTR/D（2）受体相互作用。通过NT诱导的纹状体突触前和突触后水平D（2）介导信号的减少，DA传递转向D（1）介导的传递，导致纹状体-苍白球和纹状体-黑质GABA通路的活性增加。前一种作用将导致NT治疗时出现的运动抑制和僵住症，并成为使用NT受体拮抗剂作为帕金森病治疗策略的基础。黑质NT通过在DA细胞体和树突中的拮抗NTR/D（2）受体相互作用，也可能增加黑质DA释放，导致黑质-丘脑GABA通路的D（2）介导抑制。相反，这种作用将导致抗帕金森病的作用。因此，NT传递的增加对运动系统的影响将取决于其在基底神经节中发生增加的位置。
