Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.
Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.
复制标题
DOI：
10.1523/jneurosci.0378-10.2010
复制
发表时间：
2010-03-24
期刊：
影响因子：
--
通讯作者：
Tabarean IV
中科院分区：
文献类型：
--
作者：
Lundius EG;Sanchez-Alavez M;Ghochani Y;Klaus J;Tabarean IV
视前区/下丘脑前部（PO/AH）是一个包含控制体温调节神经元的区域，是组胺影响体温的主要位点。在这里，我们报道了组胺通过激活H3亚型组胺受体来降低gaba能视前神经元的自发放电率。这种效应涉及细胞外信号调节激酶（ERK）磷酸化水平的降低，并且不依赖于突触活性。此外，组胺作用于H1亚型受体时，非ongaba能神经元群去极化，其放电率增强。在我们的实验中，H1R受体的激活与PLC途径和细胞内储存的Ca2+释放有关。这种去极化在TTX或当快速突触电位被阻断时持续存在，这表明它代表了突触后效应。单细胞反转录-PCR分析显示，gaba能神经元群体中表达H3受体，而非gaba能细胞中表达H1受体。组胺应用于正中视前核诱导一个强大的，持久的热疗效果，是由H1或H3组胺受体亚型特异性激动剂模仿。我们的数据表明，组胺通过作用于分别表达H1和H3受体亚型的两种不同的视前神经元群来调节核心体温。
The preoptic area/anterior hypothalamus (PO/AH), a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase (ERK) and was not dependent on synaptic activity. Furthermore, a population of nonGABAergic neurons was depolarized and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca2+ release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked indicating that it represents a postsynaptic effect. Single-cell reverse transcription –PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons while H1 receptors were expressed in nonGABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons which express H1 and H3 receptor subtypes, respectively.