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[恰加斯病自身抗体与人心脏毒蕈碱受体第三细胞外结构域的相互作用。功能和病理意义]

[Interaction of chagasic autoantibodies with the third extracellular domain of the human heart muscarinic receptor. Functional and pathological implications].

作者信息

Goin J C, Pérez Leirós C, Borda E, Sterin-Borda L

机构信息

Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Facultade de Odontología, Universidad de Buenos Aires, Argentina.

出版信息

Medicina (B Aires). 1996;56(6):699-704.

PMID:9284574
Abstract

Herein we demonstrate by ELISA and immunoblotting the presence in the sera of chagasic patients of circulating autoantibodies against the third extracellular domain of human muscarinic acetylcholine receptors by using a synthetic peptide corresponding to the sequence 169-192 of the receptor. Immunoaffinity purified antipeptide antibodies displayed cardiac muscarinic activity as decreased contractility and cAMP production and increased cGMP levels. These effects were specifically blocked by the synthetic peptide and by atropine. A strong association between the existence of circulating autoantibodies and the presence of dysautonomia was shown, making these autoantibodies an appropriate marker of heart autonomic dysfunction.

摘要

在此,我们通过酶联免疫吸附测定(ELISA)和免疫印迹法证明,恰加斯病患者血清中存在针对人毒蕈碱型乙酰胆碱受体第三细胞外结构域的循环自身抗体,我们使用了与该受体第169 - 192位序列相对应的合成肽。免疫亲和纯化的抗肽抗体表现出心脏毒蕈碱活性,如收缩力降低、环磷酸腺苷(cAMP)生成减少以及环磷酸鸟苷(cGMP)水平升高。这些效应被合成肽和阿托品特异性阻断。循环自身抗体的存在与自主神经功能障碍之间显示出强烈关联,使得这些自身抗体成为心脏自主神经功能障碍的合适标志物。

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