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使用两种新开发的Y1和Y2受体放射性配体评估大鼠脑中[125I]亮氨酸31、脯氨酸34]PYY和[125I]PYY3-36结合位点的放射自显影分布。

Autoradiographic distribution of [125I]Leu31,Pro34]PYY and [125I]PYY3-36 binding sites in the rat brain evaluated with two newly developed Y1 and Y2 receptor radioligands.

作者信息

Dumont Y, Fournier A, St-Pierre S, Quirion R

机构信息

Department of Psychiatry, McGill University, Verdun, Québec, Canada.

出版信息

Synapse. 1996 Feb;22(2):139-58. doi: 10.1002/(SICI)1098-2396(199602)22:2<139::AID-SYN7>3.0.CO;2-E.

DOI:10.1002/(SICI)1098-2396(199602)22:2<139::AID-SYN7>3.0.CO;2-E
PMID:8787130
Abstract

The peptide YY derivatives [Leu31,Pro34]PYY and PYY3-36 are highly selective Y1 and Y2 agonists, devoid of activity on the Y3 receptor subtype [Dumont et al. (1994) Molec. Brain Res., 26:3220-3324]. These selective ligands were iodinated and used to evaluate the respective quantitative autoradiographic distribution of the Y1 and Y2 receptor subtypes in the rat brain, excluding a potential contamination from Y3 receptor. Specific [125I][Leu31,Pro34]PYY (Y1), and [125I]PYY3-36 (Y2) binding sites are detected in various brain regions, but each showed a differential distribution profile. Y1/[125I][Leu31,Pro34]PYY sites are especially concentrated in superficial layers of the cortex, the olfactory tubercle, islands of Calleja, tenia tecta, molecular layer of the dentate gyrus, several thalamic nuclei, and the posterior part of the medial mammaliary nucleus. These areas generally contained only low densities of Y2/[125I]PYY3-36 binding sites. In contrast, [125I]PYY3-36 binding is most abundant in multiple other regions including the lateral septum, piriform cortex, triangular septal nucleus, bed nucleus of the stria terminalis, oriens layer and stratum radiatum of the dorsal hippocampus, ventral tegmental area, substantia nigra, dorsal raphe nucleus, and the granular cell layer of the cerebellum. Few areas of the rat brain contained significant amounts of both [125I][Leu31,Pro34]PYY and [125I]PYY3-36 binding sites such as the anterior olfactory nuclei, oriens layer and stratum radiatum of the ventral hippocampus, nucleus tractus solitarius, area postrema, and inferior olive. Taken together, these results and the use of two selective radioligands demonstrate further the discrete, differential distribution of the Y1 and Y2 receptor subtypes in the rat brain.

摘要

肽YY衍生物[Leu31,Pro34]PYY和PYY3-36是高度选择性的Y1和Y2激动剂,对Y3受体亚型无活性[杜蒙特等人(1994年),《分子脑研究》,26:3220 - 3324]。这些选择性配体经碘化后用于评估大鼠脑中Y1和Y2受体亚型各自的定量放射自显影分布,排除Y3受体的潜在污染。在不同脑区检测到特异性的[125I][Leu31,Pro34]PYY(Y1)和[125I]PYY3-36(Y2)结合位点,但各自呈现出不同的分布模式。Y1/[125I][Leu31,Pro34]PYY位点尤其集中在皮质浅层、嗅结节、卡耶哈岛、终纹床核、齿状回分子层、多个丘脑核以及内侧乳头体核后部。这些区域通常仅含有低密度的Y2/[125I]PYY3-36结合位点。相反,[125I]PYY3-36结合在多个其他区域最为丰富,包括外侧隔核、梨状皮质、三角隔核、终纹床核、背侧海马的原层和辐射层、腹侧被盖区、黑质、背侧中缝核以及小脑颗粒细胞层。大鼠脑内很少有区域同时含有大量的[125I][Leu31,Pro34]PYY和[125I]PYY3-36结合位点,如前嗅核、腹侧海马的原层和辐射层、孤束核、最后区以及下橄榄核。综上所述,这些结果以及两种选择性放射性配体的使用进一步证明了大鼠脑中Y1和Y2受体亚型的离散、差异分布。

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