Detailed mapping of the histamine H-2 receptor and its gene transcripts in guinea-pig brain
Detailed mapping of the histamine H-2 receptor and its gene transcripts in guinea-pig brain
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DOI：
10.1016/s0306-4522(97)00010-9
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发表时间：
1997-09-01
期刊：
影响因子：
3.3
通讯作者：
Schwartz, JC
中科院分区：
文献类型：
--
作者：
Vizuete, ML;Traiffort, E;Schwartz, JC
本文用放射自显影技术研究了豚鼠脑组织中组胺H-2受体及其信使RNA的分布，分别用[I-125]iodoaminopotentidine作放射配体结合和P-33标记的互补RNA探针作原位杂交。这两种探针进行了验证，通过评估非特异性标记使用非放射性竞争H-2受体配体和正义探针的结合位点和基因转录，分别。在某些领域，例如，大脑皮层、海马复合体或小脑，通过鉴定乳液浸渍切片上表达H受体信使RNA的神经元来完成这些研究。来自可比水平的Nissl染色切片用于定位脑结构。在许多脑区，H-2受体及其信使RNA的分布似乎与已知的组胺能轴突平行。例如，在已知接受丰富的组胺能投射的纹状体和边缘区检测到高水平的H1受体标记物。相反，在隔，下丘脑，脑桥和几个丘脑核，一个相对较低的密度的H-2受体标记物被检测到，这表明组胺在这些领域的行动是由H-1和/或H-3受体介导的。一般来说，H-2受体信使RNA的分布与[I-125]iodoaminopotentidine结合位点的分布相关性很好，尽管观察到一些差异。在一些地区（例如，黑质，蓝斑）高或中等密度的结合位点伴随着H-2受体转录物的更受限制的表达。相反，乳头区和脑桥核表现出更高水平的杂交比结合位点。在海马，大脑和小脑皮质有一个选择性定位的H-2受体信使RNA的颗粒细胞的齿状回，锥体细胞的阿蒙的角和大脑皮质，小脑浦肯野细胞，而[I-125] iodoaminopotentedine结合位点位于这些信使RNA表达神经元的树突树延伸的层。信使RNA和结合位点之间的相同差异表明纹状体黑质末梢被赋予H-2受体。组胺H-1和H-2受体似乎都存在于几个脑区，在某些情况下，这表明它们可能由相同的神经元群体共同表达，例如，在海马结构的颗粒细胞和锥体细胞中。这种共表达解释了协同反应，例如，对cAMP生成的影响，先前在两种受体亚型的共刺激后观察到。H-2受体的广泛分布，即在丘脑核或在端脑区域，如大脑皮层的大多数层，连同其兴奋作用先前在电生理学研究中建立，支持其所谓的功能，在介导组胺驱动的控制唤醒机制。此外，检测脑干区域中的H-2受体表达，从该脑干区域发出参与控制睡眠和觉醒状态的其它单胺能通路，例如，几个中缝核，蓝斑或无名质，表明所有这些系统之间可能存在相互关系，高度分歧的投射到丘脑和端脑。目前的定位H-2受体及其基因转录本应促进神经化学，神经生理学和行为学的研究，旨在澄清组胺能系统在大脑中的作用。(C)1997年IBRO。出版社：Elsevier Science Ltd
Autoradiographic studies of the distribution of the histamine H-2 receptor and its messenger RNAs were performed on serial frontal and a few sagittal sections of guinea-pig brain using [I-125]iodoaminopotentidine for radioligand binding and a P-33-labelled complementary RNA probe for in situ hybridization, respectively. Both probes were validated by assessing non-specific labelling using non radioactive competing H-2 receptor ligands and a sense probe for binding sites and gene transcripts, respectively. In some areas, e.g., cerebral cortex, hippocampal complex or cerebellum, such studies were completed by identification of neurons expressing the H receptor messenger RNAs on emulsion-dipped sections. Nissl-stained sections from comparable levels were used to localize brain structures. In many brain areas, the distribution of the H-2 receptor and its messenger RNAs appeared to parallel that known for histaminergic axons. For instance, high levels of both H, receptor markers were detected in striatal and limbic areas known to receive abundant histaminergic projections. In contrast, in septum, hypothalamic, pontine and several thalamic nuclei, a comparatively low density of both H-2 receptor markers was detected, suggesting that histamine actions in these areas are mediated by H-1 and/or H-3 receptors. Generally, the distribution of H-2 receptor messenger RNA correlates well with that of [I-125]iodoaminopotentidine binding sites, although some differences were observed. In a few regions (e.g., substantia nigra, locus coeruleus) high or moderate densities of binding sites were accompanied by a much more restricted expression of H-2 receptor transcripts. Conversely, the mammillary region and the pontine nucleus exhibited higher levels of hybridization than of binding sites. In hippocampus, cerebral and cerebellar cortex there was a selective localization of the H-2 receptor messenger RNA in the granule cells of dentate gyrus, pyramidal cells of the Ammon's horn and cerebral cortex, and Purkinje cells of cerebellum, whereas [I-125]iodoaminopotentidine binding sites were located in layers where the dendritic trees of these messenger RNA-expressing neurons extend. The same discrepancy between messenger RNAs and binding sites suggests that striatonigral endings are endowed with the H-2 receptor. The histamine H-1 and H-2 receptors both appear to be present in several brain areas, in some cases in a way suggesting their potential co-expression by the same neuronal populations, e.g., in granule and pyramidal cells in the hippocampal formation. This co-expression accounts for synergic responses, e.g., on cAMP generation, previously observed upon co-stimulation of both receptor subtypes. The widespread distribution of the H-2 receptor, namely in thalamic nuclei or in telencephalic areas such as most layers of the cerebral cortex, together with its excitatory role previously established in electrophysiological studies, support its alleged function in mediating the histamine-driven control of arousal mechanisms. In addition, the detection of H-2 receptor expression in brainstem areas from which other monoaminergic pathways involved in the control of states of sleep and wakefulness emanate, e.g., several raphe nuclei, locus coeruleus or substantia innominata, suggests possible interrelationships between all of these systems with highly divergent projections to the thalamus and telencephalon.The present mapping of the H-2 receptor and its gene transcripts should facilitate neurochemical, neurophysiological and behavioural studies aimed at clarifying the role of histaminergic systems in brain. (C) 1997 IBRO. Published by Elsevier Science Ltd.