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针对纯化的毒蕈碱受体的单克隆抗体表现出类似激动剂的活性。

Monoclonal antibodies to purified muscarinic receptor display agonist-like activity.

作者信息

Leiber D, Harbon S, Guillet J G, André C, Strosberg A D

出版信息

Proc Natl Acad Sci U S A. 1984 Jul;81(14):4331-4. doi: 10.1073/pnas.81.14.4331.

DOI:10.1073/pnas.81.14.4331
PMID:6087318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC345582/
Abstract

Monoclonal antibody M-35, which immunoprecipitates native calf brain acetylcholine muscarinic receptor, mimics agonist stimulation of the intact guinea pig myometrium: the antibody, just like carbamoylcholine hydrochloride, causes a rise in intracellular cyclic GMP content, an inhibition of cyclic AMP accumulation due to prostacyclin, and induces uterine contractions. Another antibody, M-23, which reacts with the denatured muscarinic receptor, is devoid of agonist-like activity at the cyclic nucleotide level but is still able to induce contractions of both rat and guinea pig myometrium. The cyclic nucleotide changes caused by both carbamoylcholine and antibody M-35 are inhibited by atropine; this antagonist, which blocks carbamoylcholine-mediated contractions, fails however, to prevent contractions induced by antibodies M-35 and M-23. These results suggest that the information necessary to transmit muscarinic signals is entirely contained in the receptor and that ligands only act to trigger the biological response. The data also imply that the muscarinic receptors of the myometrium are coupled to multiple effector systems.

摘要

单克隆抗体M - 35可免疫沉淀天然小牛脑乙酰胆碱毒蕈碱受体,它模拟了完整豚鼠子宫肌层的激动剂刺激作用:该抗体与盐酸氨甲酰胆碱一样,可导致细胞内环鸟苷酸(cGMP)含量升高,抑制前列环素引起的环磷酸腺苷(cAMP)积累,并诱导子宫收缩。另一种抗体M - 23可与变性的毒蕈碱受体发生反应,在环核苷酸水平上没有激动剂样活性,但仍能诱导大鼠和豚鼠子宫肌层收缩。氨甲酰胆碱和抗体M - 35引起的环核苷酸变化均被阿托品抑制;这种拮抗剂可阻断氨甲酰胆碱介导的收缩,但却无法阻止抗体M - 35和M - 23诱导的收缩。这些结果表明,传递毒蕈碱信号所需的信息完全包含在受体中,而配体仅起到触发生物学反应的作用。数据还表明,子宫肌层的毒蕈碱受体与多种效应系统偶联。

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Monoclonal antibodies to purified muscarinic receptor display agonist-like activity.针对纯化的毒蕈碱受体的单克隆抗体表现出类似激动剂的活性。
Proc Natl Acad Sci U S A. 1984 Jul;81(14):4331-4. doi: 10.1073/pnas.81.14.4331.
2
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本文引用的文献

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Agonist-mediated conformational changes of muscarinic receptors in rat brain.激动剂介导的大鼠脑内毒蕈碱受体的构象变化。
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