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抗人M2毒蕈碱受体肽抗体对豚鼠心室中环磷酸腺苷生成系统的影响。

Effects of anti-peptide antibodies against human M2 muscarinic receptors on the cAMP generating system in guinea pig ventricles.

作者信息

Wang W Z, Zhao R R, Zhu L, Jin X H, Hjalmarson A, Fu M L

机构信息

Department of Physiology, Shanxi Medical University, Taiyuan, China.

出版信息

Blood Press Suppl. 1996;3:22-4.

PMID:8973763
Abstract

The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on the cAMP generating system in guinea pig ventricles were studied. These effects were compared with those of the muscarinic receptor agonist carbachol (Carb). It was shown that: (1) both Carb and Ab were able to inhibit the isoproterenol (Iso)-stimulated cAMP production of ventricles in a dose-dependent manner. Carb at 2 microM, 10 microM and 50 microM decreased Iso-stimulated cAMP production by 8.0 +/- 1.1, 15.8 +/- 1.2 and 28.4 +/- 1.7%, respectively; whereas Ab at 50 nM, 100 nM and 400 nM decreased it by 5.8 +/- 0.4, 16.8 +/- 1.4 and 30.6 +/- 2.5%, respectively. (2) Both Carb and Ab could also inhibit the basal cAMP content of ventricles significantly. Carb at 10 microM and Ab at 100 nM decreased it by 46.9 +/- 4.2% and 60.2 +/- 4.6%, respectively. (3) The inhibitory effects of both Ab and Carb on Iso-stimulated cAMP production were significantly prevented by atropine at 1.5 microM. (4) The inhibitory effect of Ab at 100 nM was almost completely abolished by the peptide (700 nM) used as immunogen. These findings suggest that the antibodies exhibit a stimulatory muscarinic activity similar to carbachol in the inhibitory modulation of cAMP production.

摘要

研究了抗人毒蕈碱受体2第二细胞外环的抗肽抗体(Ab)对豚鼠心室中环磷酸腺苷(cAMP)生成系统的影响。将这些影响与毒蕈碱受体激动剂卡巴胆碱(Carb)的影响进行了比较。结果表明:(1)Carb和Ab均能以剂量依赖的方式抑制异丙肾上腺素(Iso)刺激的心室cAMP生成。2微摩尔、10微摩尔和50微摩尔的Carb分别使Iso刺激的cAMP生成减少8.0±1.1%、15.8±1.2%和28.4±1.7%;而50纳摩尔、100纳摩尔和400纳摩尔的Ab分别使其减少5.8±0.4%、16.8±1.4%和30.6±2.5%。(2)Carb和Ab也均能显著抑制心室的基础cAMP含量。10微摩尔的Carb和100纳摩尔的Ab分别使其减少46.9±4.2%和60.2±4.6%。(3)1.5微摩尔的阿托品可显著阻断Ab和Carb对Iso刺激的cAMP生成的抑制作用。(4)用作免疫原的肽(700纳摩尔)几乎完全消除了100纳摩尔Ab的抑制作用。这些发现表明,在对cAMP生成的抑制调节中,抗体表现出与卡巴胆碱相似的刺激性毒蕈碱活性。

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