Shi W X, Bunney B S
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510.
Synapse. 1991 Nov;9(3):157-64. doi: 10.1002/syn.890090302.
The effects of neurotensin on midbrain dopamine neuron activity were studied in brain slices using single-unit recording techniques. At low concentrations (0.2-10 nM), neurotensin attenuated dopamine-induced inhibition without a significant effect on the basal firing rate. At higher concentrations (greater than 10 nM), however, it consistently caused an increase in cell activity. At even higher concentrations (greater than 100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of neurotensin was due to depolarization inactivation or to a toxic effect of the peptide at high concentrations remains to be determined. To determine whether the effects of neurotensin were mediated by formation of a neurotensin-dopamine complex, several neurotensin analogues were studied. Neurotensin (8-13), which binds to both neurotensin receptors and dopamine, mimicked the effects of native neurotensin. Neuromedin N, which competes with neurotensin for the same receptor but does not bind to dopamine, also mimicked the effects. However, neurotensin (1-11), which forms a complex with dopamine but is inactive in competing for neurotensin receptors, was ineffective. In addition, the excitatory effect of neurotensin was not attenuated in the presence of dopamine receptor blockade by sulpiride. These results suggest that formation of a neurotensin-dopamine complex may not account for the action of neurotensin on dopamine cells. When combined with the fact that there is a high density of neurotensin receptors on dopamine cells, our results support the suggestion that the observed effects of neurotensin on dopamine neurons are most likely mediated by an activation of neurotensin receptors.
利用单单位记录技术在脑片中研究了神经降压素对中脑多巴胺能神经元活动的影响。在低浓度（0.2 - 10 nM）时，神经降压素减弱了多巴胺诱导的抑制作用，而对基础放电率无显著影响。然而，在较高浓度（大于10 nM）时，它持续导致细胞活动增加。在更高浓度（大于100 nM）时，观察到细胞活动突然停止，之前放电率有所增加。神经降压素的这种作用是由于去极化失活还是高浓度下该肽的毒性作用仍有待确定。为了确定神经降压素的作用是否由神经降压素 - 多巴胺复合物的形成介导，研究了几种神经降压素类似物。与神经降压素受体和多巴胺都结合的神经降压素（8 - 13）模拟了天然神经降压素的作用。与神经降压素竞争相同受体但不与多巴胺结合的神经介素N也模拟了这种作用。然而，与多巴胺形成复合物但在竞争神经降压素受体方面无活性的神经降压素（1 - 11）无效。此外，在存在舒必利阻断多巴胺受体的情况下，神经降压素的兴奋作用并未减弱。这些结果表明，神经降压素 - 多巴胺复合物的形成可能无法解释神经降压素对多巴胺细胞的作用。结合多巴胺细胞上存在高密度神经降压素受体这一事实，我们的结果支持以下观点：观察到的神经降压素对多巴胺神经元的作用很可能是由神经降压素受体的激活介导的。
