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大鼠脑中胰岛素样生长因子-1(生长调节素-C)受体:分布及其与海马胆碱能系统的相互作用

Insulin-like growth factor-1 (somatomedin-C) receptors in the rat brain: distribution and interaction with the hippocampal cholinergic system.

作者信息

Araujo D M, Lapchak P A, Collier B, Chabot J G, Quirion R

机构信息

Douglas Hospital Research Center, Montreal, Que., Canada.

出版信息

Brain Res. 1989 Apr 10;484(1-2):130-8. doi: 10.1016/0006-8993(89)90355-7.

Abstract

The present work characterizes the autoradiographic distribution of insulin-like growth factor-1 (IGF-1)/somatomedin-C binding sites in neonatal and adult rat brain, and attempts to correlate the distribution of IGF-1 sites, in certain regions of the rat brain, with functional IGF-1 receptors. In neonatal brain, [125I]IGF-1 binding sites are especially concentrated in superficial cortical layers, nucleus accumbens and hippocampus. In the adult rat brain, the distribution of IGF-1 sites is broader, with a high density of sites observed in superficial and deep cortical layers, olfactory bulb, endopiriform nucleus, basomedial nucleus of the amygdala, thalamic nuclei and hippocampus. Specific binding of [125I]IGF-1 to its sites in these brain regions was almost completely inhibited by 100 nM nonradioactive IGF-1. In contrast, similar concentrations of either IGF-2 or insulin did not significantly alter [125I]IGF-1 binding to its sites. Therefore, under our incubation conditions, [125I]IGF-1 appears to label specifically the type-I IGF receptor. In the hippocampus, which is highly enriched with specific [125I]IGF-1 binding sites in both neonatal and adult rat brain, IGF-1 significantly altered the potassium-evoked (25 mM) release of acetylcholine (ACh) from slices of adult, but not immature (6- and 18-day-old), rat brain. This IGF-1-induced decrease in ACh release from adult rat brain slices was concentration-dependent and appeared to be specific to hippocampus; ACh release from frontal cortical slices was not affected by this GF. The spontaneous release of ACh in the presence of IGF-1 in either tissue was not significantly different from control.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

本研究对新生和成年大鼠脑中胰岛素样生长因子-1(IGF-1)/生长调节素-C结合位点的放射自显影分布进行了表征,并试图将大鼠脑某些区域中IGF-1位点的分布与功能性IGF-1受体相关联。在新生脑中,[125I]IGF-1结合位点特别集中在皮质浅层、伏隔核和海马体。在成年大鼠脑中,IGF-1位点的分布更广泛,在皮质浅层和深层、嗅球、内梨状核、杏仁核基底内侧核、丘脑核和海马体中观察到高密度的位点。100 nM非放射性IGF-1几乎完全抑制了[125I]IGF-1在这些脑区与其位点的特异性结合。相比之下,类似浓度的IGF-2或胰岛素并未显著改变[125I]IGF-1与其位点的结合。因此,在我们的孵育条件下,[125I]IGF-1似乎特异性标记了I型IGF受体。在新生和成年大鼠脑中都富含特异性[125I]IGF-1结合位点的海马体中,IGF-1显著改变了成年大鼠脑切片中钾离子诱发(25 mM)的乙酰胆碱(ACh)释放,但未改变未成熟(6日龄和18日龄)大鼠脑切片中的释放。IGF-1诱导的成年大鼠脑切片中ACh释放减少呈浓度依赖性,且似乎对海马体具有特异性;额叶皮质切片中的ACh释放不受该生长因子的影响。在任一组织中,IGF-1存在时ACh的自发释放与对照无显著差异。(摘要截断于250字)

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