Agnati L F, Fuxe K
Biosci Rep. 1983 Dec;3(12):1101-5. doi: 10.1007/BF01120202.
By means of the dopamine (DA) agonist radio ligand 3H-N-propylnorapomorphine (3H-NPA) the effects of cholecystokinin-8 (CCK-8) have been evaluated in vitro on the binding characteristics of the DA agonist sites in membrane preparations from the subcortical limbic forebrain containing mainly nucleus accumbens and tuberculum olfactorium. It was shown that CCK-8 (10(-8) M) can produce a 40% increase in the KD value of the 3H-NPA binding sites and a significant 10% increase in the Bmax values of these sites. It is therefore suggested that there exist marked receptor-receptor interactions between the CCK-8 binding sites and DA agonist binding sites in the limbic forebrain. On the basis of these findings and in view of the fact that CCK peptides are comodulators in certain types of mesolimbic DNA neurons but cannot modulate DA release in these DNA synapses, the hypothesis is introduced that the presence of DA comodulators such as CCK-8 in the DA synapses makes possible a heterostatic regulation of the synapse. Thus, by means of receptor-receptor interactions, peptide comodulators may change the set point of the main transmission line without inducing homeostatic feedback responses on synthesis and release of the main transmitter, opening up a new way to modulate chemical transmission in general.
通过多巴胺（DA）激动剂放射性配体3H-N-丙基去甲阿朴吗啡（3H-NPA），已在体外评估了胆囊收缩素-8（CCK-8）对主要包含伏隔核和嗅结节的皮质下边缘前脑膜制剂中DA激动剂位点结合特性的影响。结果表明，CCK-8（10^(-8) M）可使3H-NPA结合位点的KD值增加40%，并使这些位点的Bmax值显著增加10%。因此，提示边缘前脑中CCK-8结合位点与DA激动剂结合位点之间存在明显的受体-受体相互作用。基于这些发现，并鉴于CCK肽在某些类型的中脑边缘多巴胺能神经元中是共调节剂，但不能调节这些多巴胺能突触中的DA释放这一事实，提出了这样的假说：DA突触中存在如CCK-8这样的DA共调节剂使得对突触进行异稳态调节成为可能。因此，通过受体-受体相互作用，肽共调节剂可以改变主要传输线路的设定点，而不会在主要递质的合成和释放上诱导稳态反馈反应，从而总体上开辟了一种调节化学传递的新途径。
