Tanganelli S, Li X M, Ferraro L, Von Euler G, O'Connor W T, Bianchi C, Beani L, Fuxe K
Department of Pharmacology, University of Ferrara, Italy.
Eur J Pharmacol. 1993 Jan 12;230(2):159-66. doi: 10.1016/0014-2999(93)90798-m.
Combined perfusion of the neostriatum with 1 nM of cholecystokinin octapeptide (CCK-8) and 0.01, 0.1 or 1 nM of neurotensin was done in the halothane-anesthetized rat after systemic apomorphine treatment (0.05 mg/kg, s.c.). Neurotensin (1 nM) plus CCK-8 (1 nM) effectively counteracted the apomorphine-induced inhibition of neostriatal perfusate levels of dopamine (DA). With a constant concentration of CCK-8 (1 nM), the apomorphine-induced inhibition of DA release was counteracted dose relatedly by neurotensin in concentrations of 0.01, 0.1 and 1 nM. The results of binding experiments demonstrated that threshold concentrations of CCK-8 and neurotensin significantly increased the KD values of the high-affinity D2 receptors without significant alterations in the low-affinity D2 receptors or in the proportion of D2 receptors in the high-affinity state. Thus, neurotensin and CCK receptors may regulate synergistically, via intramembrane interactions with the D2 receptors, the binding characteristics and the signal transduction of D2 autoreceptors in the neostriatum. The combined presence of very low concentrations of CCK-8 and neurotensin in the extracellular fluid may be sufficient to regulate D2 receptor transduction, underlining the important role of these peptide receptor interactions with the D2 receptors.
在经全身注射阿扑吗啡（0.05mg/kg，皮下注射）处理后的氟烷麻醉大鼠中，将1nM的胆囊收缩素八肽（CCK-8）与0.01、0.1或1nM的神经降压素联合灌注到新纹状体中。神经降压素（1nM）加CCK-8（1nM）可有效对抗阿扑吗啡诱导的新纹状体灌流液中多巴胺（DA）水平的抑制。在CCK-8浓度恒定为1nM时，阿扑吗啡诱导的DA释放抑制被浓度为0.01、0.1和1nM的神经降压素剂量依赖性地对抗。结合实验结果表明，CCK-8和神经降压素的阈浓度显著增加了高亲和力D2受体的KD值，而低亲和力D2受体或高亲和力状态下D2受体的比例没有明显改变。因此，神经降压素和CCK受体可能通过与D2受体的膜内相互作用协同调节新纹状体中D2自身受体的结合特性和信号转导。细胞外液中极低浓度的CCK-8和神经降压素共同存在可能足以调节D2受体转导，突显了这些肽受体与D2受体相互作用的重要作用。
