Integrated research of histamine system from molecular to wholeanimals and humans using leading-edge technologies

本研究利用前沿技术，研究了尚未完全溶解的神经元组胺的新作用。本研究是在分子和细胞水平及全动物实验上进行的，我们试图将结果直接与转化人类PET研究联系起来。本研究的主要发现如下：1)阐明了c -末端在H3受体介导的信号转导中的作用；2)组胺在中枢神经系统中的转运是通过星形胶质细胞中一种新发现的非特异性t转运体PMAT（质膜单胺转运体）介导的。3)首次发现H3受体在胰岛细胞中的存在及其作用。4)用组胺受体敲除小鼠研究组胺受体在全动物行为水平上的作用。5)利用分子PET显像研究H1受体占用期抗组胺药的脑药动学。

Using leading-edge te chnologies, this study examined new roles of neuronal histamine which have not been fully dissolved. This study was performed on the experiments of molecular and cellular levels and whole animals, and we attempted the results were directly connected to tra nslational human PET studies. Main findings of this study are as follows : 1)The role of C-terminal on H3 receptors-mediated signal transduction were clarified ; 2)The transport of histamine in the CNS was mediated through a newly-identified non-specific t ransporter, PMAT (plasma membrane monoamine transporter)in astrocytes. 3)The existence and roles of H3 receptors in pancreatic islet cells were discovered for the first time. 4)The roles of histamine receptors on whole animals' behavioral levels were ex amined using histamine receptors knockout mice. 5)Brain pharmacokinetics of antihistamines was revealed using molecular PET imaging on the term of H1 receptor occupancy.