抗M_2受体的抗肽段抗体对cAMP产生量和钙电流的影响  

Effects of anti-peptide antibodies against the second extracellular loop of human M_2 muscarinic receptors on the cAMP production and calcium currents

作　　者：王文泽[1] 赵荣瑞[2] 吴博威[2] 郭光伟[1] 唐进[1] 李家成[1] Hjalmarson Ake Michael Fu LX 

机构地区：[1]山西医科大学第二临床医学院心胸外科,太原030001 [2]山西医科大学生理学教研室 [3]瑞典哥德堡大学,Sahlgren医院,Wallenberg实验室

出　　处：《山西医科大学学报》2001年第z1期39-42,共4页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目!( 3 93 70 3 0 4)

摘　　要：应用放射免疫分析方法及全细胞膜片钳技术研究了抗M2 受体细胞外第二环上的抗肽段抗体 (Abs )对豚鼠心室肌细胞cAMP产生量和内向钙电流 (ICa)的影响并同M受体激动剂的效应进行了比较。结果如下 :M受体激动剂carbachol(Carb10 μmol/L)和抗肽段抗体 (Abs 10 0nmol/L)两者均可抑制异丙肾上腺素 (Iso 0 .8μmol/L)所引起的cAMP量的增加〔Carb可使组织中cAMP从 (10 8.2± 7.0 )降为 (88.4± 7.2 )pmol/ (mg·min) ,Abs可使组织中cAMP从 (10 8.2± 7.0 )降为 (88.6± 5 .1)pmol/ (mg·min)〕及ICa的增加〔Carb可使ICa从 (5 3.5± 7 0 ) %降为 (13.0± 2 0 ) % ,而Abs可使ICa从 (6 6 .9± 10 .5 ) %降为(34 .5± 8 0 ) %〕。M受体阻断剂阿托品 (Atr)可以阻断Carb和Abs的以上效应。以上结果提示 :此抗肽段抗体同M受体激动剂一样可以通过减少 β受体激动剂所引起的cAMP的增加从而达到降低 β受体激动剂所引起的ICa的增加 ,由此可以对心室肌M2 受体产生作用。以上结果进一步提示自身免疫有可能参与了特发性扩张性心肌病的发病过程 ,而M2 受体细胞外第二环上的氨基酸肽段可能为免疫反应的靶作用区。Effects of anti peptide antibodies against the second extracellular loop of human M 2 muscarinic receptors on the cAMP production and calcium currents(I Ca ) in guinea pig ventricular myocytes were studied by using radioimmunoassay and whole cell patch clamp technique and a comparison was also made with those of the muscarinic receptor agonist. Both muscarinic receptor agonist carbachol (Carb 10 μmol/L) and anti peptide antibodies (Abs 100 nmol/L) could decrease the isoprenaline (Iso 0.8 μmol/L) induced increases of cAMP〔from (108.2±7.0) to (88.4±7.2) pmol/(mg·min)for Carb and (88.6±5.1) pmol/(mg·min) for Abs respectively〕 production and increases of I Ca 〔from (53.5± 7.0)% to (13.0±2.0)% for Carb and (66.9± 10.5)% to (34.5±8.0)% for Abs respectively〕. The muscarinic receptor antagonist atropine (Atr) was able to prevent these effects of Carb and Abs.These results indicated that the anti peptide antibodies against an epitope located in the second extracellular loop of human M 2 muscarinic receptors, similar to muscarinic receptor agonist, could decrease the β receptor agonist stimulated increase of I Ca by decreasing the β receptor agonist stimulated increase of cAMP productions and therefore could have an effect on their target receptor. These results further suggest that autoimmunity may participate in the pathogenesis of human idiopathic dilated cardiomyopathy(DCM) and the second extracellular loop of human M 2 musarinic receptor could be the main immunodominant region.

关 键 词：抗体 抗肽段 受体 毒蕈碱 腺苷环一磷酸 

分 类 号：R338.8[医药卫生—人体生理学]