Miñano F J, Peinado J M, Myers R D
Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.
Peptides. 1988 Nov-Dec;9(6):1381-7. doi: 10.1016/0196-9781(88)90206-9.
This investigation was undertaken in the unrestrained rat to determine the localized effect of neurotensin (NT) on the profile of release and turnover of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) within the hypothalamus. Following stereotaxic implantation of a permanent guide tube, artificial CSF was perfused in the hypothalamus of the freely moving animal by means of push-pull cannulae at a rate of 20 microliters/min and for an interval of 5.0 min. After three 5.0 min control samples were collected, NT in a concentration of 0.1 micrograms/microliter was perfused followed by additional CSF controls. Assay by HPLC-EC of each perfusate showed that when the rat was sated, NT evoked a significant increase in the release of DA and DOPAC from the hypothalamus as well as augmented NE turnover, as reflected by a significant efflux in MHPG. However, when the rat was fasted for 22 hr, the perfusion of NT reduced DA and DOPAC concentrations in the diencephalic perfusate significantly as well as levels of both MHPG and VMA. Under both sated and fasted conditions, NT failed to produce notable changes in the release of 5-HT or its metabolism to 5-HIAA. These findings thus reveal a functional interaction between NT and both of the catecholamine neurotransmitters within hypothalamic neurons, which is clearly dependent upon the nutritional status of the animal.
本研究在未受限制的大鼠身上进行，以确定神经降压素（NT）对下丘脑去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）释放及周转情况的局部影响。在立体定位植入永久性引导管后，通过推挽式套管以20微升/分钟的速率在下丘脑对自由活动动物灌注人工脑脊液，持续5.0分钟。在收集三个5.0分钟的对照样本后，灌注浓度为0.1微克/微升的NT，随后再进行脑脊液对照。通过高效液相色谱-电化学检测法对每个灌流液进行分析表明，当大鼠处于饱食状态时，NT引起下丘脑DA和3,4-二羟基苯乙酸（DOPAC）释放显著增加，同时NE周转增强，这表现为3-甲氧基-4-羟基苯乙二醇（MHPG）显著流出。然而，当大鼠禁食22小时时，灌注NT显著降低了间脑灌流液中DA和DOPAC的浓度以及MHPG和香草扁桃酸（VMA）的水平。在饱食和禁食两种条件下，NT均未使5-HT的释放或其代谢为5-羟吲哚乙酸（5-HIAA）产生显著变化。因此，这些发现揭示了NT与下丘脑神经元内两种儿茶酚胺神经递质之间的功能相互作用，这种相互作用明显依赖于动物的营养状态。
