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阿尔茨海默型痴呆患者血小板中I2-咪唑啉受体与单胺氧化酶B活性之间的解离。

Dissociation between I2-imidazoline receptors and MAO-B activity in platelets of patients with Alzheimer's type dementia.

作者信息

Soto J, Ulibarri I, Jauregui J V, Ballesteros J, Meana J J

机构信息

Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia, Spain.

出版信息

J Psychiatr Res. 1999 May-Jun;33(3):251-7. doi: 10.1016/s0022-3956(98)00065-x.

Abstract

The I2-imidazoline receptor is expressed in brain and platelets and could represent a new binding domain on MAO-B enzyme. Brain I2-imidazoline receptors and MAO-B sites have been found to be increased in Alzheimer's disease. The study sought to evaluate I2-imidazoline receptors and MAO-B activity in platelets from patients with Alzheimer's type dementia (ATD) and matched controls. Preliminary saturation experiments of [3H]idazoxan binding to platelet purified mitochondrial membranes were performed to determine the maximal number of binding sites (Bmax) and the apparent dissociation constant (Kd). Afterwards, the I2-imidazoline receptor density ([3H]idazoxan at 8 and 20 nM in the presence of 2 x 10(-6) M efaroxan) was evaluated in 20 patients with ATD and 17 controls. MAO-B activity was quantified by [14C]PEA oxidation. All subjects were screened for cognitive evaluation by the Mini-Mental State Examination. The density of I2-imidazoline receptors was similar in ATD patients (8.4 and 14.3 fmol/mg protein) and controls (8.3 and 14.0 fmol/mg protein). MAO-B activity was 22% higher in ATD subjects. Significant correlations between I2-imidazoline receptors and MAO-B activity were observed. No relationships between I2-imidazoline receptors or MAO-B activity and the cognitive score were observed. In conclusion, platelet I2-imidazoline receptors do not show the increase of I2-imidazoline receptors previously observed in brain of subjects with ATD. The dissociation between I2-imidazoline receptors and MAO-B in platelets suggests that the enzyme contributes to but not exclusively represents the I2-imidazoline receptor.

摘要

I2-咪唑啉受体在大脑和血小板中表达,可能代表单胺氧化酶B(MAO-B)酶上的一个新结合域。已发现阿尔茨海默病患者大脑中的I2-咪唑啉受体和MAO-B位点有所增加。该研究旨在评估阿尔茨海默型痴呆(ATD)患者和匹配对照组血小板中的I2-咪唑啉受体及MAO-B活性。进行了[3H]伊达唑胺与血小板纯化线粒体膜结合的初步饱和实验,以确定结合位点的最大数量(Bmax)和表观解离常数(Kd)。之后,在20例ATD患者和17例对照组中评估I2-咪唑啉受体密度(在2×10⁻⁶ M依发罗新存在下,8 nM和20 nM的[3H]伊达唑胺)。通过[14C]苯乙胺氧化对MAO-B活性进行定量。所有受试者均通过简易精神状态检查表进行认知评估筛查。ATD患者(8.4和14.3 fmol/mg蛋白)和对照组(8.3和14.0 fmol/mg蛋白)的I2-咪唑啉受体密度相似。ATD受试者的MAO-B活性高22%。观察到I2-咪唑啉受体与MAO-B活性之间存在显著相关性。未观察到I2-咪唑啉受体或MAO-B活性与认知评分之间的关系。总之,血小板I2-咪唑啉受体并未表现出先前在ATD受试者大脑中观察到的I2-咪唑啉受体增加情况。血小板中I2-咪唑啉受体与MAO-B之间的分离表明,该酶对I2-咪唑啉受体有作用,但并非唯一代表I2-咪唑啉受体。

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