Durieux C, Pélaprat D, Charpentier B, Morgat J L, Roques B P
Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté de Pharmacie, Paris.
Neuropeptides. 1988 Oct;12(3):141-8. doi: 10.1016/0143-4179(88)90045-5.
We have investigated the possible occurrence of distinct CCK8 and CCK4 binding sites in the brain by comparing the binding characteristics of [3H] CCK4 to those of the CCK8 analogue, [3H] Boc (Nle28,31]CCK27-33 (BDNL-CCK7). [3H] CCK4 and [3H] BNDL-CCK7 were shown to interact with mouse brain membranes with very similar maximal binding capacities 31.7 +/- 2.1 fmol/mg prot (KD = 3.78 +/- 0.47 nM) and 38.9 +/- 2.2 fmol/mg prot (KD = 0.26 +/- 0.02 nM) respectively. The apparent affinities of five CCK analogues for the sites labelled by both probes were almost identical. Autoradiographic studies revealed that the distribution of [3H] CCK4 binding sites in rat forebrain was the same as that of [3H] BDNL-CCK7, with high densities of receptors in the cortex, nucleus accumbens, olfactory bulb and the medial striatum, moderate densities in the amygdala, the hippocampus, several nuclei of the thalamus and hypothalamus. However in the interpenduncular nucleus where there was moderate binding of [3H]BDNL-CCK7, no [3H]CCK4 labelling was observed. These studies demonstrated the occurrence of one class of high affinity binding sites for [3H] CCK4 in mouse and rat brain, with characteristics similar to those already reported with CCK33, CCK8 and pentagastrin probes. Nevertheless the presence of a small amount of very high affinity binding sites for [3H]CCK4 cannot be excluded.
我们通过比较[3H]CCK4与CCK8类似物[3H]Boc（Nle28,31]CCK27 - 33（BDNL - CCK7）的结合特性，研究了大脑中不同CCK8和CCK4结合位点存在的可能性。结果显示，[3H]CCK4和[3H]BDNL - CCK7与小鼠脑膜相互作用时，具有非常相似的最大结合容量，分别为31.7±2.1 fmol/mg蛋白（KD = 3.78±0.47 nM）和38.9±2.2 fmol/mg蛋白（KD = 0.26±0.02 nM）。两种探针标记的位点对五种CCK类似物的表观亲和力几乎相同。放射自显影研究表明，大鼠前脑中[3H]CCK4结合位点的分布与[3H]BDNL - CCK7相同，在皮质、伏隔核、嗅球和内侧纹状体中受体密度高，在杏仁核、海马、丘脑和下丘脑的几个核中密度适中。然而，在脚间核中，[3H]BDNL - CCK7有中等程度的结合，但未观察到[3H]CCK4标记。这些研究表明，在小鼠和大鼠脑中存在一类[3H]CCK4的高亲和力结合位点，其特性与已报道的CCK33、CCK8和五肽胃泌素探针类似。不过，不能排除存在少量[3H]CCK4的极高亲和力结合位点。
