Gehlert D R, Gackenheimer S L
CNS Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Neuroscience. 1997 Jan;76(1):215-24. doi: 10.1016/s0306-4522(96)00340-5.
The distribution of neuropeptide Y Y1 and Y2 receptors has been extensively studied in the rat using selective masking of [125I]peptide YY binding by Y1- and Y2-selective peptides. In the present study, we characterized the binding of the subtype-selective radioligands 125I-peptide YY and [125I]peptide YY3-36 to rat and guinea-pig brains and identified differences in Y1 and Y2 distribution. 125I-peptide YY and [125I]peptide YY3-36 bound to single sites in rat and guinea-pig brains with pharmacologies consistent with the Y1 and Y2 receptors, respectively. Autoradiographic studies were conducted using adjacent sections from rat and guinea-pig brains. Compared to the rat, the distribution of both Y1 and Y2 receptors was markedly different in the guinea-pig. For example, a high level of Y1 binding was detected within the thalamus of the rat while, in the guinea-pig, very little Y1 binding was observed in this region. Y1 binding was very low in the rat hippocampus, while the guinea-pig hippocampus contained high levels of Y1 binding. High levels of both Y1 and Y2 binding were observed in the guinea-pig cerebellum while, in the rat, only low levels of Y2 binding were visible. Therefore, the guinea-pig brain exhibits dramatic differences in the pattern of Y1 and Y2 receptors when compared to the rat. It is likely that Y1 and Y2 receptors perform different roles in the central nervous system of guinea-pigs and rats.
利用Y1和Y2选择性肽对[125I]肽YY结合的选择性掩盖,已在大鼠中广泛研究了神经肽Y Y1和Y2受体的分布。在本研究中,我们对亚型选择性放射性配体125I-肽YY和[125I]肽YY3-36与大鼠和豚鼠脑的结合进行了表征,并确定了Y1和Y2分布的差异。125I-肽YY和[125I]肽YY3-36分别与大鼠和豚鼠脑中的单一位点结合,其药理学特性分别与Y1和Y2受体一致。使用大鼠和豚鼠脑的相邻切片进行放射自显影研究。与大鼠相比,豚鼠中Y1和Y2受体的分布明显不同。例如,在大鼠丘脑内检测到高水平的Y1结合,而在豚鼠中,该区域几乎未观察到Y1结合。大鼠海马中的Y1结合非常低,而豚鼠海马中含有高水平的Y1结合。在豚鼠小脑中观察到高水平的Y1和Y2结合,而在大鼠中,仅可见低水平的Y2结合。因此,与大鼠相比,豚鼠脑在Y1和Y2受体模式上表现出显著差异。Y1和Y2受体可能在豚鼠和大鼠的中枢神经系统中发挥不同作用。