Ferraro L, O'Connor W T, Antonelli T, Fuxe K, Tanganelli S
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Eur J Neurosci. 1997 Sep;9(9):1838-46. doi: 10.1111/j.1460-9568.1997.tb00750.x.
In the present dual-probe microdialysis study the effects of intrastriatal perfusion with the tridecapeptide neurotensin(1-13) [NT(1-13)] and its active fragment NT(8-13) on striatopallidal GABA and striatal dopamine release were investigated. The modulatory action of NT(1-13) on D2 receptor-mediated inhibition of striatal and pallidal GABA release was also studied. Both intrastriatal NT(1-13) (100 nM) and NT(8-13) (100 nM) increased striatal (139 and 149% respectively) and pallidal (130 and 164%) GABA release, and this effect was antagonized by intrastriatal perfusion with the neurotensin receptor antagonist SR48692 (100 nM). A similar increase (155%) in striatal dopamine release was observed following intrastriatal NT(1-13) (100 nM), but not NT(8-13) (100 and 500 nM). However, at the highest concentration studied (1 microM) NT(8-13) was associated with a rapid increase (130%) in striatal dopamine release. In a second study intrastriatal NT(1-13) (10 nM) counteracted the inhibition of striatal and pallidal GABA release induced by pergolide (500 and 1500 nM). The inhibitory action of the D2 agonist was restored when SR48692 (100 nM) was added to the perfusion medium. These results suggest that in the neostriatum the neurotensin receptor located postsynaptically on the striatopallidal GABA neurons seems to differ from the neurotensin receptor located on dopaminergic terminals, as indicated by the relative lack of effect of NT(8-13) on striatal dopamine release. Furthermore, the ability of NT(1-13) to counteract the pergolide-induced inhibition of both striatal and pallidal GABA release strengthens the evidence for antagonistic receptor-receptor interaction between postsynaptic striatal neurotensin and D2 receptors located on striatopallidal GABA neurons.
在本双探针微透析研究中，研究了纹状体内灌注十三肽神经降压素（1-13）[NT（1-13）]及其活性片段NT（8-13）对纹状体苍白球γ-氨基丁酸（GABA）和纹状体多巴胺释放的影响。还研究了NT（1-13）对D2受体介导的纹状体和苍白球GABA释放抑制的调节作用。纹状体内灌注NT（1-13）（100 nM）和NT（8-13）（100 nM）均增加了纹状体（分别为139%和149%）和苍白球（130%和164%）的GABA释放，且这种作用被纹状体内灌注神经降压素受体拮抗剂SR48692（100 nM）所拮抗。纹状体内灌注NT（1-13）（100 nM）后观察到纹状体多巴胺释放有类似的增加（155%），但NT（8-13）（100和500 nM）则未观察到。然而，在研究的最高浓度（1 μM）下，NT（8-13）与纹状体多巴胺释放的快速增加（130%）有关。在第二项研究中，纹状体内灌注NT（1-13）（10 nM）抵消了培高利特（500和1500 nM）诱导的纹状体和苍白球GABA释放的抑制作用。当将SR48692（100 nM）添加到灌注培养基中时，D2激动剂的抑制作用得以恢复。这些结果表明，在新纹状体中，位于纹状体苍白球GABA能神经元突触后的神经降压素受体似乎与位于多巴胺能终末的神经降压素受体不同，这一点由NT（8-13）对纹状体多巴胺释放相对缺乏作用所表明。此外，NT（1-13）抵消培高利特诱导的纹状体和苍白球GABA释放抑制的能力，加强了突触后纹状体神经降压素与位于纹状体苍白球GABA能神经元上的D2受体之间存在拮抗受体-受体相互作用的证据。
