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单胺氧化酶A缺陷小鼠中咪唑啉结合位点的放射自显影分布

Autoradiographical distribution of imidazoline binding sites in monoamine oxidase A deficient mice.

作者信息

Anderson Neil J, Seif Isabelle, Nutt David J, Hudson Alan L, Robinson Emma S J

机构信息

Department of Pharmacology, School of Medical Sciences, Bristol, UK.

出版信息

J Neurochem. 2006 Mar;96(6):1551-9. doi: 10.1111/j.1471-4159.2006.03662.x. Epub 2006 Feb 10.

Abstract

This study has used receptor autoradiography to characterize imidazoline binding sites (I-BS) in monoamine oxidase (MAO) A knockout and wild-type mice. A comparison between MAO-A and MAO-B, binding of the endogenous beta-carboline [(3)H]harmane, and I-BS, has been made using sections from brain and kidney. The loss of binding to MAO-A in the knockout animals was confirmed using the selective radioligand [(3)H]Ro41-1049, with labelling reduced to background levels. The binding of [(3)H]Ro19-6327 to MAO-B was unaffected, indicating no change in this isoform in response to the loss of MAO-A. A reduction in binding to the I(2)-BS, as labelled by both [(3)H]idazoxan and [(3)H]2-BFI (2-(2-benzofuranyl)-2-imidazoline), was seen in the MAO-A knockout animals in both brain and kidney sections, whereas binding to the I(1)-BS in kidney sections remained unchanged. The loss of I(2) binding was found to be regionally dependent and was positively correlated with the relative expression of MAO-A in specific regions in the wild-type animals. Using the MAO-A knockout mice it was also possible to demonstrate a non-MAO-A population of binding sites labelled by the putative I-BS endogenous ligand, harmane.

摘要

本研究利用受体放射自显影技术对单胺氧化酶(MAO)A基因敲除小鼠和野生型小鼠体内的咪唑啉结合位点(I-BS)进行了表征。使用脑和肾组织切片,对MAO-A和MAO-B、内源性β-咔啉[(3)H]哈尔满的结合以及I-BS进行了比较。使用选择性放射性配体[(3)H]Ro41-1049证实了基因敲除动物中MAO-A结合的丧失,标记减少至背景水平。[(3)H]Ro19-6327与MAO-B的结合未受影响,表明该同工型在MAO-A缺失时没有变化。在MAO-A基因敲除动物的脑和肾切片中,观察到由[(3)H]异喹唑和[(3)H]2-BFI(2-(2-苯并呋喃基)-2-咪唑啉)标记的I(2)-BS结合减少,而肾切片中与I(1)-BS的结合保持不变。发现I(2)结合的丧失具有区域依赖性,并且与野生型动物特定区域中MAO-A的相对表达呈正相关。利用MAO-A基因敲除小鼠,还能够证明由假定的I-BS内源性配体哈尔满标记的非MAO-A结合位点群体。

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