Vilaró M Teresa, Cortés Roser, Mengod Guadalupe
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain.
J Comp Neurol. 2005 Apr 18;484(4):418-39. doi: 10.1002/cne.20447.
Serotonin 5-HT4 receptors are widely distributed in the periphery and in brain, where they modulate the release of various neurotransmitters and have been implicated in learning and memory. Nine C-terminal splice variants of this receptor have been cloned in mammalian species. In the rat, three such variants have been described: 5-HT4(a), 5-HT4(b), and 5-HT4(e). In the present study, we have examined several aspects of the distribution of these receptors in brain. First, we provide, in rat and guinea pig, a detailed comparison of the distribution of 5-HT4 receptors labeled by the antagonist [125I]-SB 207710 with the distribution of their encoding mRNA visualized by in situ hybridization histochemistry (ISHH). The results suggest that, in several projection systems (striato-nigral and striato-pallidal pathways, projection from dentate granule cells to field CA3, habenulo-interpeduncular pathway), 5-HT4 receptors are located both somatodendritically and axonally. Second, we have analyzed the distribution of mRNA for the three known rat splice variants by reverse transcription-polymerase chain reaction (RT-PCR) and by ISHH. RT-PCR indicates that all three variants are widely distributed, with 5-HT4(b) mRNA being present in all regions examined (olfactory tubercle, striatum, hippocampus, inferior colliculus, substantia nigra, parietal cortex) and 5-HT4(a) and 5-HT4(e) showing a somewhat more restricted distribution. In other regions (periaqueductal gray, reticular formation, medial septum, diagonal band), faint ISHH signals are observed for 5-HT4(a)+4(e) mRNAs, whereas 5-HT4(b) mRNA signals are almost undetectable. Finally, neurotoxic lesions of basal ganglia components in guinea pig also indicate a location of these receptors on terminals of striatal projection neurons.
5-羟色胺5-HT4受体广泛分布于外周和大脑中，在那里它们调节各种神经递质的释放，并与学习和记忆有关。该受体的9种C末端剪接变体已在哺乳动物中克隆出来。在大鼠中，已描述了三种这样的变体：5-HT4(a)、5-HT4(b)和5-HT4(e)。在本研究中，我们研究了这些受体在大脑中的分布的几个方面。首先，我们在大鼠和豚鼠中，详细比较了拮抗剂[125I]-SB 207710标记的5-HT4受体的分布与通过原位杂交组织化学（ISHH）可视化的其编码mRNA的分布。结果表明，在几个投射系统（纹状体-黑质和纹状体-苍白球通路、齿状颗粒细胞到CA3区的投射、缰核-脚间通路）中，5-HT4受体既位于胞体树突上，也位于轴突上。其次，我们通过逆转录-聚合酶链反应（RT-PCR）和ISHH分析了三种已知大鼠剪接变体的mRNA分布。RT-PCR表明，所有三种变体都广泛分布，5-HT4(b) mRNA存在于所有检测区域（嗅结节、纹状体、海马体、下丘、黑质、顶叶皮质），而5-HT4(a)和5-HT4(e)的分布则略显局限。在其他区域（导水管周围灰质、网状结构、内侧隔、斜角带），观察到5-HT4(a)+4(e) mRNA的ISHH信号较弱，而5-HT4(b) mRNA信号几乎无法检测到。最后，豚鼠基底神经节成分的神经毒性损伤也表明这些受体位于纹状体投射神经元的终末。
