Takechi H, Matsumura K, Watanabe Y, Kato K, Noyori R, Suzuki M, Watanabe Y
Subfemtomole Biorecognition Project, Research Development Corporation of Japan, Osaka 565, Japan.
J Biol Chem. 1996 Mar 8;271(10):5901-6. doi: 10.1074/jbc.271.10.5901.
By use of several prostacyclin analogs and an in vitro autoradiographic technique, we have found a novel subtype of the prostacyclin receptor, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affinity for the novel subtype (dissociation constant (Kd) of 7.8 nM). However, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (Kd = 159 nM) for the subtype. Other prostaglandins showed no or little affinity for the subtype. [3H]Isocarbacyclin binding was high in the thalamus, lateral septal nucleus, hippocampus, cerebral cortex, striatum, and dorsal cochlear nucleus. Although the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [3H]isocarbacyclin binding, [3H]iloprost also had high affinity in these regions, and the binding specificity was similar to that for the known prostacyclin receptor. Hemilesion studies of striatal neurons lesioned by kainate or of dopaminergic afferents lesioned by 6-hydroxydopamine revealed that the binding sites of the novel subtype exist on neuronal cells in the striatum, but not on the presynaptic terminal of afferents or on glial cells. Electrophysiological studies carried out in the CA1 region of the hippocampus revealed that prostacyclin analogs have a facilitatory effect on the excitatory transmission through the novel prostacyclin receptor. The widespread expression of the prostacyclin receptor in the central nervous system suggests that prostacyclin has important roles in neuronal activity.
通过使用几种前列环素类似物和体外放射自显影技术，我们发现了一种新型的前列环素受体亚型，其结合特性与大鼠脑中已知的前列环素受体不同。异前列环素是已知前列环素受体的强效激动剂，对该新型亚型具有高亲和力（解离常数（Kd）为7.8 nM）。然而，通常用作稳定前列环素类似物的伊洛前列素对该亚型显示出低亲和力结合（Kd = 159 nM）。其他前列腺素对该亚型没有或几乎没有亲和力。[3H]异前列环素结合在丘脑、外侧隔核、海马、大脑皮层、纹状体和背侧耳蜗核中较高。虽然孤束核和三叉神经脊束核显示出高密度的[3H]异前列环素结合，但[3H]伊洛前列素在这些区域也具有高亲和力，并且结合特异性与已知前列环素受体相似。对由海藻酸损伤的纹状体神经元或由6-羟基多巴胺损伤的多巴胺能传入神经进行的半侧损伤研究表明，新型亚型的结合位点存在于纹状体的神经元细胞上，而不存在于传入神经的突触前末端或胶质细胞上。在海马CA1区进行的电生理研究表明，前列环素类似物通过新型前列环素受体对兴奋性传递具有促进作用。前列环素受体在中枢神经系统中的广泛表达表明前列环素在神经元活动中具有重要作用。
