Staudt A, Mobini R, Fu M, Grosse Y, Stangl V, Stangl K, Thiele A, Baumann G, Felix S B
Klinik für Innere Medizin B, Medizinische Fakultät, Ernst-Moritz-Arndt-Universität, Fr.-Loefflerstr. 23a, D-17487 Greifswald, Germany.
Eur J Pharmacol. 2001 Jul 6;423(2-3):115-9. doi: 10.1016/s0014-2999(01)01113-x.
beta(1)-Adrenoceptor autoantibodies are present in approximately 30% of patients suffering from dilated cardiomyopathy. The inotropic effects mediated by these antibodies remain to be studied. Monoclonal antibodies were raised against a peptide corresponding to the second extracellular loop of the human beta(1)-adrenoceptor in balb/C mouse (n=6), and were characterized by enzyme immunoassay after purification by protein A. Purified immunoglobulin G from non-immunized animals (controls) did not influence Ca(2+) transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)-adrenoceptor antibodies caused a dose-related increase in Ca(2+) transient (dilution 1:2: +35.3+/-5.1%), and in cell shortening (dilution 1:2: +40.5+/-6.3%) (P<0.01 vs. controls). The effect of the beta(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol. In addition, beta(1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic adenosine monophosphate. The inotropic response induced by isoproterenol was attenuated by the beta(1)-adrenoceptor antibody. beta(1)-adrenoceptor antibodies as partial agonists induce a specific positive inotropic effect via the protein-kinase-A-cascade.
在大约30%的扩张型心肌病患者中存在β1 -肾上腺素能受体自身抗体。这些抗体介导的正性肌力作用仍有待研究。在6只Balb/C小鼠中制备了针对与人β1 -肾上腺素能受体第二个细胞外环对应的肽段的单克隆抗体，并在通过蛋白A纯化后用酶免疫测定法对其进行表征。来自未免疫动物（对照）的纯化免疫球蛋白G不影响通过共聚焦激光扫描显微镜测量的大鼠心肌细胞的Ca2+瞬变和细胞缩短。β1 -肾上腺素能受体抗体导致Ca2+瞬变呈剂量相关增加（稀释1:2时增加35.3±5.1%），以及细胞缩短呈剂量相关增加（稀释1:2时增加40.5±6.3%）（与对照相比，P<0.01）。β1 -肾上腺素能受体抗体的作用被抗原肽和拮抗剂美托洛尔阻断。此外，β1 -肾上腺素能受体抗体诱导环磷酸腺苷呈剂量依赖性增加。异丙肾上腺素诱导的正性肌力反应被β1 -肾上腺素能受体抗体减弱。β1 -肾上腺素能受体抗体作为部分激动剂通过蛋白激酶A级联反应诱导特异性正性肌力作用。
