Boersma C J, Pool C W, Van Heerikhuize J J, Van Leeuwen F W
Graduate School of Neurosciences, Amsterdam, The Netherlands.
J Neuroendocrinol. 1994 Feb;6(1):47-56. doi: 10.1111/j.1365-2826.1994.tb00554.x.
Previous studies have suggested an involvement of enkephalins in regulation of oxytocin (OXT) and vasopressin (AVP) release, which seems to disagree with the very low affinities of Met- and Leu-enkephalin for the kappa opioid receptor. As opioid receptors in the neural lobe exclusively exist of kappa receptors, we studied the binding characteristics of larger pro-enkephalin derived peptides for opioid binding sites in the neural lobe by means of light microscopic receptor autoradiography. In addition, the pharmacological characteristics of opioid binding sites in the neural lobe were compared with those in other parts of the pituitary. In the neural as well as the intermediate lobe both high and low affinity 3H-bremazocine binding sites were present. Binding to these sites was completely displaceable by both naloxone and nor-binaltorphimine suggesting that these sites represent kappa opioid receptors. Also with regard to selectivity and affinity characteristics to other ligands, opioid binding sites in the neural and intermediate lobe were quite similar. In the anterior lobe a very low level of bremazocine binding was present, which could not be displaced by nor-binaltorphimine. Displacement studies with pro-enkephalin and pro-dynorphin derived peptides showed that both groups of peptides could bind to opioid binding sites in the neural and intermediate lobe. Especially the relatively large pro-dynorphin and pro-enkephalin derived peptides, such as dynorphin 1-17 and BAM22, appeared to be very potent ligands for these opioid binding sites and were much more potent than smaller fragments, such as dynorphin 1-8, and Met- and Leu-enkephalin. These results contradict the existence of a mismatch in the neural (and intermediate) lobe with regard to the local type of opioid peptides and receptors present.
先前的研究表明脑啡肽参与催产素（OXT）和加压素（AVP）释放的调节，这似乎与甲硫氨酸脑啡肽和亮氨酸脑啡肽对κ阿片受体的极低亲和力不一致。由于神经叶中的阿片受体仅为κ受体，我们通过光学显微镜受体放射自显影术研究了较大的前脑啡肽衍生肽与神经叶中阿片结合位点的结合特性。此外，还将神经叶中阿片结合位点的药理学特性与垂体其他部位的进行了比较。在神经叶和中间叶中均存在高亲和力和低亲和力的3H-布马佐辛结合位点。纳洛酮和去甲双丙戊酰吗啡均可完全取代与这些位点的结合，这表明这些位点代表κ阿片受体。就对其他配体的选择性和亲和力特性而言，神经叶和中间叶中的阿片结合位点也非常相似。在前叶中，布马佐辛结合水平非常低，且不能被去甲双丙戊酰吗啡取代。用前脑啡肽和前强啡肽衍生肽进行的置换研究表明，这两组肽均可与神经叶和中间叶中的阿片结合位点结合。尤其是相对较大的前强啡肽和前脑啡肽衍生肽，如强啡肽1-17和BAM22，似乎是这些阿片结合位点的非常有效的配体，并且比较小的片段，如强啡肽1-8、甲硫氨酸脑啡肽和亮氨酸脑啡肽更有效。这些结果与神经叶（和中间叶）中存在的阿片肽和受体的局部类型不匹配的观点相矛盾。
