Distribution, regulation and role of hypothalamic galanin systems: Renewed interest in a pleiotropic peptide family
Distribution, regulation and role of hypothalamic galanin systems: Renewed interest in a pleiotropic peptide family
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DOI：
10.1046/j.1440-1681.2001.03411.x
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发表时间：
2001-01-01
影响因子：
2.9
通讯作者：
Larm, JA
中科院分区：
文献类型：
--
作者：
Gundlach, AL;Burazin, TCD;Larm, JA
1.已知甘丙肽和甘丙肽受体结合位点广泛分布在中枢神经系统内，特别是在视前区的下丘脑、室旁核（PVN）和视上核（SON）以及弓状核/正中隆起中。本文就甘丙肽及其两种受体亚型mRNA的区域和细胞定位的研究进展作一简要综述（GalR 1和GalR 2），生理刺激对各种核团中甘丙肽和/或甘丙肽受体表达的调节，甘丙肽对下丘脑神经元的电生理学作用，以及甘丙肽样肽（Galanin-like peptide，GALP）的分离和克隆，GALP是GalR 2的一种假定的内源性配体，3。大细胞核（m）和小细胞核（p）PVN和背内侧核、腹内侧核和弓状核。相比之下，GalR 2 mRNA在pPVN中富集，但在mPVN中不富集，并且在SON中未检测到。此外，GalR 2 mRNA存在于背内侧核中，并且与GalR 1转录物相比在弓状核中富集，在所有亚群中具有许多标记细胞。4，SON和PVN的神经元含有加压素和/或催产素，沿着几种其他肽，并且这些激素和肽的产生和释放受到各种生理刺激的调节。关于甘丙肽系统，GalR 1和甘丙肽表达通过盐负荷在大细胞神经元中增加，并且通过泌乳下调，这与甘丙肽在渗透刺激后对加压素释放的抑制增加和泌乳期间对催产素释放的抑制减少一致。甘丙肽对电刺激的强抑制作用（和分泌）大细胞神经元的活性和甘丙肽对离体弓状核中谷氨酸突触释放的复杂突触前作用表明多种甘丙肽受体亚型在这些下丘脑的调节中起着积极的作用。猪下丘脑中一种多肽的分离（GALP-1-60），其在结构上与甘丙肽相关并且似乎对GalR 2的选择性超过GalR 1，以及随后从猪克隆GALP cDNA，大鼠和人类应该允许研究帮助揭示甘丙肽受体亚型所起的生理作用（特别是GalR 2）及其多个配体在下丘脑和其他脑区域中的作用。
1. Galanin peptide and galanin receptor-binding sites are known to be widely distributed within the central nervous system, particularly in the hypothalamus in the preoptic area, the paraventricular (PVN) and supraoptic (SON) nuclei and the arcuate nucleus/median eminence.2, The present brief review focuses on some recent studies of the regional and cellular localization of mRNA encoding galanin and two galanin receptor subtypes (GalR1 and GalR2) in the hypothalamus, regulation of galanin and/or galanin receptor expression in various nuclei by physiological stimuli, electrophysiological effects of galanin on hypothalamic neurons and the isolation and cloning of galanin-like peptide (GALP), a putative endogenous ligand for GalR2,3, In situ hybridization studies in rat brain have demonstrated an abundance of GalR1 mRNA in SON, magnocellular (m) and parvocellular (p) PVN and dorsomedial, ventromedial and arcuate nuclei. In contrast, GalR2 mRNA is enriched in pPVN, but not mPVN, and is not detected in SON. In addition, GalR2 mRNA is present in the dorsomedial nucleus and is enriched in the arcuate nucleus compared with GalR1 transcripts, with numerous labelled cells in all subdivisions.4, Neurons of the SON and PVN contain vasopressin and/or oxytocin, along with several other peptides, and the production and release of these hormones and peptides are modulated by various physiological stimuli. In relation to galanin systems, GalR1 and galanin expression is increased in magnocellular neurons by salt loading and is downregulated by lactation, consistent with an increased inhibition by galanin of vasopressin release following osmotic stimulation and a decreased inhibition of oxytocin release during lactation.5, Powerful inhibitory effects of galanin on the electrical (and secretory) activity of magnocellular neurons and complex presynaptic actions of galanin on the synaptic release of glutamate in the arcuate nucleus in vitro suggest an active role for multiple galanin receptor subtypes in the regulation of these hypothalamic systems in vitro.6, The recent isolation of a peptide from porcine hypothalamus (GALP-1-60) that is structurally related to galanin and appears to be selective for GalR2 over GalR1 and the subsequent cloning of GALP cDNA from pig, rat and humans should allow studies to help reveal the physiological role played by galanin receptor subtypes (especially GalR2) and their multiple ligands in the hypothalamus and other brain areas.