Montaudon E, Abdelkrim M A, Desfontis J-C, Mallem M Y
LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France.
LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France.
Ann Cardiol Angeiol (Paris). 2014 Jun;63(3):128-34. doi: 10.1016/j.ancard.2014.04.011. Epub 2014 Apr 28.
To analyze vascular reactivity changes in response to immunization protocols with antigens corresponding to the second extracellular loop of -β3 and -β1 and 3 adrenergic receptors (AR).
Lewis rats were immunized for 3months with peptidic sequences corresponding to the second extracellular loop of β3-AR or β1 and 3-AR. Specific β3-AR antibodies were characterized by Elisa and purified using "Proteus Protein G" kit. Their functionality were tested in rabbit isolated ventricular cardiomyocytes. Aortic and mesenteric artery rings isolated from control or immunized rats were mounted in organ baths and precontracted with phenylephrine. Then, relaxant curves were established.
SR58611A (10nM), a preferential β3-AR agonist and purified β3-AR antibodies (25μg/mL) induced a decrease of cell shortening (-39.56±4.4% [n=11] and -18.45±3.9% [n=10] respectively) in isolated cardiomyocytes. This decrease was significantly inhibited when the cardiomyocytes were pre-incubated with the L-748337 (1μM), a selective β3-AR antagonist (P<0.05). In contrast with what was observed in rats immunized against the β1-AR, vasorelaxations induced by acetylcholine and SR58611A in both aorta and mesenteric arteries were unaltered in rats immunized against the β3-AR and β1 and 3-AR.
These results show, for the first time, that β3-AR antibodies induced a β3-AR agonist-like activity. They would not have a vascular pathogenic action but would offset the endothelial dysfunction caused by β1-AR antibodies.
分析用与β3和β1及3肾上腺素能受体（AR）的第二个细胞外环相对应的抗原进行免疫方案后血管反应性的变化。
用与β3-AR或β1和3-AR的第二个细胞外环相对应的肽序列对Lewis大鼠进行3个月的免疫。通过酶联免疫吸附测定法（ELISA）对特异性β3-AR抗体进行鉴定，并用“变形杆菌蛋白G”试剂盒进行纯化。在兔离体心室心肌细胞中测试其功能。将从对照或免疫大鼠分离的主动脉和肠系膜动脉环安装在器官浴槽中，并用去氧肾上腺素进行预收缩。然后，建立舒张曲线。
SR58611A（10 nM），一种选择性β3-AR激动剂和纯化的β3-AR抗体（25μg/mL）分别在离体心肌细胞中引起细胞缩短减少（分别为-39.56±4.4%[n = 11]和-18.45±3.9%[n = 10]）。当心肌细胞与选择性β3-AR拮抗剂L-748337（1μM）预孵育时，这种减少受到显著抑制（P<0.05）。与针对β1-AR免疫的大鼠中观察到的情况相反，在针对β3-AR和β1及3-AR免疫的大鼠中，乙酰胆碱和SR58611A在主动脉和肠系膜动脉中诱导的血管舒张未发生改变。
这些结果首次表明，β3-AR抗体诱导了类似β3-AR激动剂的活性。它们不会具有血管致病作用，但会抵消由β1-AR抗体引起的内皮功能障碍。
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