Lapchak P A, Araujo D M, Quirion R, Beaudet A
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
J Neurochem. 1991 Feb;56(2):651-7. doi: 10.1111/j.1471-4159.1991.tb08199.x.
The effects of neurotensin (NT) alone or in combination with the dopamine antagonist sulpiride were tested on the release of endogenous acetylcholine (ACh) from striatal slices. NT enhanced potassium (25 mM)-evoked ACh release from striatal slices in a dose-dependent manner. This effect was tetrodotoxin-insensitive, suggesting an action directly on cholinergic elements. The dopamine antagonist sulpiride (5 x 10(-5) M) significantly increased (63%) potassium-evoked ACh release from striatal slices; potassium-evoked ACh release was further increased (90%) in the presence of NT (10(-5) M) and sulpiride (5 x 10(-5) M). The second set of experiments tested the effects of 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra on NT-induced increases of potassium-evoked ACh release. These lesions did not alter the NT regulation of potassium-evoked ACh release from striatal slices, but did significantly increase spontaneous (33%) and potassium-evoked (40%) ACh release from striatal slices. Striatal choline acetyltransferase activity was not affected by 6-OHDA lesions. In addition, following 6-OHDA lesions, sulpiride was ineffective in altering ACh release from striatal slices. Furthermore, evoked ACh release in the presence of the combination of NT and sulpiride was not different from that in the presence of NT alone. These results suggest that in the rat striatum, NT regulates cholinergic interneuron activity by interacting with NT receptors associated with cholinergic elements. Moreover, the NT modulation of cholinergic activity is independent of either an interaction of NT with D2 dopamine receptors or the sustained release of dopamine.
研究了神经降压素（NT）单独作用或与多巴胺拮抗剂舒必利联合作用对纹状体切片内源性乙酰胆碱（ACh）释放的影响。NT以剂量依赖的方式增强了钾（25 mM）诱发的纹状体切片中ACh的释放。这种作用对河豚毒素不敏感，提示其直接作用于胆碱能元件。多巴胺拮抗剂舒必利（5×10⁻⁵ M）显著增加了钾诱发的纹状体切片中ACh的释放（增加63%）；在NT（10⁻⁵ M）和舒必利（5×10⁻⁵ M）存在的情况下，钾诱发的ACh释放进一步增加（增加90%）。第二组实验测试了黑质6-羟基多巴胺（6-OHDA）损伤对NT诱导的钾诱发ACh释放增加的影响。这些损伤并未改变NT对纹状体切片中钾诱发ACh释放的调节，但确实显著增加了纹状体切片中自发的（增加33%）和钾诱发的（增加40%）ACh释放。纹状体胆碱乙酰转移酶活性不受6-OHDA损伤的影响。此外，6-OHDA损伤后，舒必利对改变纹状体切片中ACh的释放无效。此外，在NT和舒必利联合存在时诱发的ACh释放与单独存在NT时诱发的ACh释放没有差异。这些结果表明，在大鼠纹状体中，NT通过与胆碱能元件相关的NT受体相互作用来调节胆碱能中间神经元的活性。此外，NT对胆碱能活性的调节独立于NT与D2多巴胺受体的相互作用或多巴胺的持续释放。
