Skomedal T, Fu M L, Hjalmarson A, Hoebeke J, Schiander I G, Osnes J B
Department of Pharmacology, University of Oslo, Norway.
Eur J Pharmacol. 1997 Aug 27;333(2-3):169-75. doi: 10.1016/s0014-2999(97)01127-8.
The modulation of the inotropic effect by affinity-purified antibodies against a synthetic peptide corresponding to the second extracellular loop of the human muscarinic M2 receptors was studied in adult rat ventricular myocardium. These anti-muscarinic M2 receptor antibodies shifted the dose-response relationship of the beta-adrenoceptor agonist isoproterenol to higher concentrations whereas preimmune rabbit immunoglobulin G (IgG) or antibodies against the N-terminus of the beta 1-adrenoceptor had no effect. This effect of anti-muscarinic M2 receptor antibodies was fully blocked after preincubation with the antigenic peptide. No significant change of maximal inotropic response to isoproterenol was observed in the presence of anti-muscarinic M2 receptor antibodies. The anti-muscarinic M2 receptor antibodies did apparently not hamper the access of the muscarinic receptor agonist carbachol. The muscarinic receptor antagonist atropine attenuated the effect of the anti-muscarinic M2 receptor antibodies. The present study demonstrates for the first time in intact adult ventricular myocardium a specific stimulatory muscarinic activity of antibodies raised against a part of the muscarinic M2 receptor protein.
在成年大鼠心室肌中，研究了针对与人毒蕈碱型M2受体第二个细胞外环相对应的合成肽的亲和纯化抗体对心肌收缩力的调节作用。这些抗毒蕈碱型M2受体抗体将β-肾上腺素能受体激动剂异丙肾上腺素的剂量反应关系向更高浓度偏移，而免疫前兔免疫球蛋白G（IgG）或针对β1-肾上腺素能受体N端的抗体则无此作用。抗毒蕈碱型M2受体抗体与抗原肽预孵育后，其作用完全被阻断。在抗毒蕈碱型M2受体抗体存在的情况下，未观察到对异丙肾上腺素最大正性肌力反应的显著变化。抗毒蕈碱型M2受体抗体显然不妨碍毒蕈碱受体激动剂卡巴胆碱的作用。毒蕈碱受体拮抗剂阿托品减弱了抗毒蕈碱型M2受体抗体的作用。本研究首次在完整的成年心室肌中证明，针对毒蕈碱型M2受体蛋白一部分产生的抗体具有特定的刺激毒蕈碱活性。
