A DETAILED AUTORADIOGRAPHIC MAPPING OF HISTAMINE-H-3 RECEPTORS IN RAT-BRAIN AREAS
A DETAILED AUTORADIOGRAPHIC MAPPING OF HISTAMINE-H-3 RECEPTORS IN RAT-BRAIN AREAS
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DOI：
10.1016/0306-4522(93)90191-h
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发表时间：
1993-01-01
期刊：
影响因子：
3.3
通讯作者：
SCHWARTZ, JC
中科院分区：
文献类型：
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作者：
POLLARD, H;MOREAU, J;SCHWARTZ, JC
[H-3](R)α-甲基组胺是一种选择性组胺 H-3 受体配体，用于与膜进行结合研究，并在大鼠大脑切片中生成光学显微镜放射自显影图。在大脑皮层前部、伏隔核、纹状体、嗅结节和黑质的膜中发现了高密度的 H-3 受体。矢状和额叶切片的放射自显影证明，在非常低的背景下，许多灰质区域中存在特异性标记，这是使用硫哌丁胺（一种选择性 H-3 受体拮抗剂）作为竞争药物进行测定的。通过与相邻的尼氏染色切片进行比较来识别标记区域，并通过视觉对它们的标记进行评级。H-3 受体在已知接收组胺能投射的区域中不均匀地分布。在大脑皮层中，H-3 受体存在于所有区域和层中，具有颈尾梯度，深层（IV-VI 层）密度较高。在海马结构中，H-3 受体在齿状回和下托中最丰富。在杏仁核复合体中，最高密度出现在中央、外侧和基底外侧的核组中。在基底前脑中，伏隔核、纹状体、嗅结节和苍白球被高度标记。在组胺能纤维稀缺的丘脑中，H-3 受体以相当高的密度存在，特别是在核的中线、正中和层内组中。在下丘脑中，组胺能纤维网络最密集，H-3 受体以中等密度存在，前部和内侧部分稍微丰富一些。它们还存在于结节乳头核水平，它们可能驻留在组胺能核周上。在中脑和下脑干中，H-3受体在黑质网状部分和中央灰质中丰富。它们以低密度存在于去甲肾上腺素能和血清素能核周区域以及脊髓中，在灰质中检测到微弱的特异性标记，特别是在背角的外层中。在小脑和垂体中，H-3 受体很少。膜结合和放射自显影研究表明，将红藻氨酸输注到纹状体后，H-3 受体局部显着减少。通过电凝外侧下丘脑区域单侧中断上行组胺能通路，随后纹状体 [H-3](R)α-甲基组胺结合同侧增加，这一过程与突触后 H-3 受体的去神经上调一致。这些病变数据，加上 H-3 受体区域分布与组胺能轴突之间观察到的差异，表明这些受体在靶细胞上比在组胺能神经元上更丰富，在组胺能神经元上它们充当自身受体。
[H-3](R)alpha-methylhistamine, a selective histamine H-3-receptor ligand, was used to perform binding studies with membranes and generate light microscopic autoradiograms in sections of the rat brain.High densities of H-3 receptors were found in membranes from the anterior part of the cerebral cortex, the accumbens nucleus, the striatum, the olfactory tubercles and the substantia nigra. Autoradiography of sagittal and frontal sections evidenced specific labelling in a number of gray matter areas over a very low background, as determined using thioperamide, a selective H-3-receptor antagonist, as competing drug. Labelled areas were identified by comparison with adjacent Nissl-stained sections and their labelling was rated visually.H-3 receptors are heterogeneously distributed among areas known to receive histaminergic projections. In the cerebral cortex, H-3 receptors are present in all areas and layers, with a rostrocaudal gradient and a higher density in deep layers (laminae IV-VI). In the hippocampal formation, H-3 receptors are the most abundant in the dentate gyrus and the subiculum. In the amygdaloid complex, the highest densities are found in the central, lateral and basolateral groups of nuclei. In the basal forebrain, the accumbens nucleus, the striatum, the olfactory tubercles and the globus pallidus are highly labelled. In the thalamus in which histaminergic fibres are scarce, H-3 receptors are present in a rather high density, particularly in the midline, median and intralaminar groups of nuclei. In the hypothalamus, where the densest network of histaminergic fibres is found, H-3 receptors occur in moderate density, being slightly more abundant in the anterior and medial part. They are also present at the level of the tuberomammillary nuclei where they may reside on histaminergic perikarya. In mesencephalon and lower brainstem, H-3 receptors are abundant in the reticular part of the substantia nigra and central gray. They are present in low density in areas of noradrenergic and serotoninergic perikarya and in the spinal cord, where a faint specific labelling is detected in the gray matter, particularly in the external layers of the dorsal horn. In the cerebellum and pituitary gland, H-3 receptors are scarce.Kainic acid infusions into the striatum were followed by marked local decreases in H-3 receptors evidenced in both membrane binding and autoradiographic studies. Unilateral interruption of the ascending histaminergic pathways via electrocoagulation of the lateral hypothalamic area was followed by ipsilateral increase in striatal [H-3](R)alpha-methylhistamine binding, a process consistent with denervation up regulation of postsynaptic H-3 receptors.These lesion data, taken together with the differences observed between the regional distribution of H-3 receptors and that of histaminergic axons, indicate that these receptors are more abundant on target cells than on histaminergic neurons where they act as autoreceptors.