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大鼠视神经中多种烟碱型乙酰胆碱受体的转运:含α6和β3亚基的受体高密度分布

Transport of multiple nicotinic acetylcholine receptors in the rat optic nerve: high densities of receptors containing alpha6 and beta3 subunits.

作者信息

Cox Brandon C, Marritt Andrea M, Perry David C, Kellar Kenneth J

机构信息

Department of Pharmacology, Georgetown University School of Medicine, Washington, Washington DC, USA.

出版信息

J Neurochem. 2008 Jun;105(5):1924-38. doi: 10.1111/j.1471-4159.2008.05282.x. Epub 2008 Feb 5.

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are abundant in the rat retina and at least seven heteromeric subtypes have been detected. Axons of retinal ganglion cells form the optic nerve and innervate areas of the brain important for visual processing, including the lateral geniculate nucleus, the superior colliculus, and the pretectal nucleus. Development of eye-specific layers in these projection areas are dependent upon retinal waves which are initially mediated by nAChRs [Feller et al., Science 272 (1996), 1182; Penn et al., Science 279 (1998), 2108; Bansal et al., J. Neurosci. 20 (2000), 7672]. Unilateral eye-enucleation studies in the rat indicate that nAChRs are on the terminals of optic nerve axons, where they may mediate influences of acetylcholine on visual pathways. In this study, we use radioligand binding and immunoprecipitation with subunit-selective antibodies to investigate the subunit composition of nAChRs in the rat optic nerve. We found multiple nAChR subtypes in the optic nerve, all of which contain the beta2 subunit. Most of these receptors are mixed heteromeric subtypes, composed of at least three different subunits. Included among these subtypes is the highest percentage and density of alpha6- and beta3-containing nAChRs of any area of the rat CNS that has been reported.

摘要

神经元烟碱型乙酰胆碱受体(nAChRs)在大鼠视网膜中大量存在,并且已检测到至少七种异聚体亚型。视网膜神经节细胞的轴突形成视神经,并支配对视觉处理很重要的脑区,包括外侧膝状体核、上丘和顶盖前核。这些投射区域中眼特异性层的发育取决于视网膜波,而视网膜波最初由nAChRs介导[费勒等人,《科学》272(1996),1182;佩恩等人,《科学》279(1998),2108;班萨尔等人,《神经科学杂志》20(2000),7672]。对大鼠进行的单侧眼球摘除研究表明,nAChRs存在于视神经轴突的末端,在那里它们可能介导乙酰胆碱对视觉通路的影响。在本研究中,我们使用放射性配体结合和亚基选择性抗体免疫沉淀法来研究大鼠视神经中nAChRs的亚基组成。我们在视神经中发现了多种nAChR亚型,所有这些亚型都含有β2亚基。这些受体中的大多数是混合异聚体亚型,由至少三种不同的亚基组成。在这些亚型中,含α6和β3的nAChRs在大鼠中枢神经系统任何区域中的比例和密度都是已报道的最高值。

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