[3H]LY334370, a novel radioligand for the 5-HT1F receptor.: II.: Autoradiographic localization in rat, guinea pig, monkey and human brain
[3H]LY334370, a novel radioligand for the 5-HT1F receptor.: II.: Autoradiographic localization in rat, guinea pig, monkey and human brain
复制标题
DOI：
10.1007/s00210-005-1036-8
复制
发表时间：
2005-03-01
影响因子：
3.6
通讯作者：
Nelson, DL
中科院分区：
文献类型：
--
作者：
Lucaites, VL;Krushinski, JH;Nelson, DL
LY334370是5-HT1F受体的高亲和力、选择性激动剂。在此基础上，考察了氚化合物在放射自显影中的应用，以定位大鼠和豚鼠脑区的5-HT1F受体。5-HT1F受体在大鼠脑内的4-5层、嗅球和结节、伏隔核、尾壳核、丘脑束旁核、乳头体内侧核、海马CA3区、下丘脑和几个杏仁核均有特异性结合。在豚鼠脑中，[H-3]LY334370结合部位在屏状核密度最高，但在皮质、尾壳核、伏隔核、丘脑和乳头体内侧核也有分布。5-HT1F受体的分布存在一定的物种差异。大鼠脑放射自显影与[H-3]LY334370和[H-3]舒马曲坦的对比显示，在相同的脑区有标记。在恒河猴和人脑切片上的初步结合研究表明，[H-3]LY334370结合在小脑的皮质4-5层、下丘脑(在猴子中)和颗粒细胞层。这些发现表明5-HT1F受体在大鼠、豚鼠、猴和人脑中有离散的定位，并证实了[H-3]LY334370可作为进一步探索5-HT1F受体的定位和可能功能的潜在工具。
LY334370 is a high affinity, selective agonist at the 5-HT1F receptor. On this basis, the tritiated compound was examined for its utility in autoradiography to localize the 5-HT1F receptor in rat and guinea pig brain regions. Specific 5-HT1F receptor binding in rat brain was found in layers 4 - 5 of all cortical regions examined, as well as olfactory bulb and tubercle, nucleus accumbens, caudate putamen, parafascicular nucleus of the thalamus, medial mammillary nucleus, the CA3 region of the hippocampus, subiculum, and several amygdaloid nuclei. In guinea pig brain, the [H-3] LY334370 binding sites were found at highest density in claustrum, but also in a layer of the cortex, caudate putamen, nucleus accumbens, thalamus, and medial mammillary nucleus. Some species differences in the distribution of the 5-HT1F receptor were noted. Side by side comparison of rat brain autoradiography with [H-3] LY334370 and [H-3] sumatriptan showed labeling in the same brain regions. Preliminary binding studies in rhesus monkey and human brain sections showed [H-3] LY334370 binding in cortical layers 4-5, subiculum ( in the monkey), and the granule cell layer of the cerebellum. These findings suggest a discrete localization of the 5-HT1F receptor in the rat, guinea pig, monkey and human brain, and confirms the utility of [H-3] LY334370 as a potential tool to explore further the localization and possible functions of the 5-HT1F receptor.