Widdowson P S
Department of Psychiatry, Case Western Reserve University, Cleveland, OH.
Brain Res. 1993 Dec 17;631(1):27-38. doi: 10.1016/0006-8993(93)91182-r.
Quantitative receptor autoradiography was performed on sections of rat and human brain using [125I]peptide YY ([125I]PYY) to measure the anatomical distribution of neuropeptide Y (NPY) receptors. Masking Y1- and Y2-NPY subtypes with the agonists (Leu31,Pro34]NPY and NPY13-36, respectively demonstrated a differential distribution of Y1 and Y2 receptors between human and rat brain. In human brain, the highest density of [125I]PYY binding was found in pyramidal layers (CA4-CA1) of hippocampus, head and tail regions of caudate nucleus, locus coeruleus and substantia nigra. There was moderate [125I]peptide YY binding to NPY receptors in the molecular layers of the hippocampus, frontal and temporal cerebral cortex, especially in superficial layers, anterior amygdala, central grey and inferior colliculus. Low levels of binding were observed in white matter. The selective Y1 receptor agonist, [Leu31,Pro34]NPY did not effectively reduce [125I]PYY binding to any human brain region examined except for approximately 20-40% of the binding sites in the molecular layer of the dentate gyrus, layer IV of the frontal cortex and the radiatum and oriens layers of the hippocampal complex. In contrast, the Y2 agonist, NPY13-36 was effective at reducing [125I]PYY binding in all human brain regions examined. In rat brain, high densities of [125I]PYY binding was measured in cerebral cortex, thalamus and inferior colliculus which was sensitive to [Leu31,Pro34]NPY. In contrast, high densities of the NPY13-36 sensitive binding was found in the hippocampus, striatum and nucleus accumbens. Medium to low densities of NPY13-36 sensitive binding was found in medulla and pons. This data suggests that human brain contains primarily Y2-type NPY receptors with only a few regions expressing Y1-type receptors. No human brain region examined contained solely Y1-type receptors. In contrast to human brain, rat brain contains regions which express only Y1 receptors as well as regions containing only Y2 receptors and regions containing both Y1 and Y2 receptors.
采用[125I]肽YY（[125I]PYY）对大鼠和人类大脑切片进行定量受体放射自显影，以测量神经肽Y（NPY）受体的解剖分布。分别用激动剂[Leu31,Pro34]NPY和NPY13 - 36掩盖Y1和Y2 - NPY亚型，结果显示人类和大鼠大脑中Y1和Y2受体的分布存在差异。在人类大脑中，[125I]PYY结合密度最高的区域是海马体的锥体细胞层（CA4 - CA1）、尾状核的头部和尾部区域、蓝斑和黑质。在海马体、额叶和颞叶皮质的分子层，尤其是表层、前杏仁核、中央灰质和下丘脑中，[125I]肽YY与NPY受体有中度结合。在白质中观察到低水平的结合。选择性Y1受体激动剂[Leu31,Pro34]NPY除了能使齿状回分子层、额叶皮质第IV层以及海马复合体的辐射层和原层中约20 - 40%的结合位点的[125I]PYY结合减少外，对所检测的任何人类脑区的[125I]PYY结合均无有效降低作用。相比之下，Y2激动剂NPY13 - 36能有效降低所有所检测人类脑区的[125I]PYY结合。在大鼠大脑中，在大脑皮质、丘脑和下丘脑中检测到高密度的[125I]PYY结合，这些区域对[Leu31,Pro34]NPY敏感。相反，在海马体、纹状体和伏隔核中发现了对NPY13 - 36敏感的高密度结合。在延髓和脑桥中发现了对NPY13 - 36敏感的中低密度结合。这些数据表明，人类大脑主要含有Y2型NPY受体，只有少数区域表达Y1型受体。所检测的人类脑区中没有一个仅含有Y1型受体。与人类大脑不同，大鼠大脑中既有仅表达Y1受体的区域，也有仅含有Y2受体的区域以及同时含有Y1和Y2受体的区域。
