INCREASE OF GI-ALPHA IN HUMAN HEARTS WITH DILATED BUT NOT ISCHEMIC CARDIOMYOPATHY
INCREASE OF GI-ALPHA IN HUMAN HEARTS WITH DILATED BUT NOT ISCHEMIC CARDIOMYOPATHY
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DOI：
10.1161/01.cir.82.4.1249
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发表时间：
1990-10-01
期刊：
影响因子：
37.8
通讯作者：
ERDMANN, E
中科院分区：
文献类型：
--
作者：
BOHM, M;GIERSCHIK, P;ERDMANN, E
在扩张型心肌病（DCM）心脏的心肌膜中，通过约40 kDa百日咳毒素底物的32 P-ADP-核糖基化测定，Gi α蛋白增加了37%。免疫印迹技术还显示DCM中Gi α的量增加。在缺血性心肌病（ICM）的心脏中，与非衰竭心肌（NF）相比，Gi α没有改变。基础和Gpp（NH）p刺激的腺苷酸环化酶活性在DCM中降低，但在ICM中不降低。与NF相比，DCM和ICM中β-肾上腺素受体的数量同样减少。未发生m-胆碱受体或A1-腺苷受体的改变。一致的是，“间接”负性肌力作用的m-胆碱受体激动剂卡巴胆碱和A1-腺苷受体激动剂R-PIA在ICM，DCM和非衰竭心肌没有不同。在ICM和DCM中，对异丙肾上腺素和米力农的正性变力反应显著降低。然而，与ICM相比，DCM进一步减少。它的结论是，Gi α的增加是伴随着基础和鸟嘌呤核苷酸刺激的腺苷酸环化酶活性的减少。m-胆碱受体和A1-腺苷受体的改变似乎不涉及。异丙肾上腺素和米力农在DCM中的正性肌力作用的进一步降低提供了证据，表明Gi α的增加在DCM中而不是ICM中具有功能相关性，因此可能有助于内源性儿茶酚胺和外源性cAMP依赖性正性肌力药物在前者而不是后者条件下的作用降低。
In myocardial membranes from hearts with dilated cardiomyopathy (DCM), there was a 37% increase of the Gi alpha-protein as measured by 32P-ADP-ribosylation of a approximately 40 kDa pertussis toxin substrate. Immunoblotting techniques also showed increased amounts of Gi alpha in DCM. In hearts with ischemic cardiomyopathy (ICM), Gi alpha was not altered compared with nonfailing myocardium (NF). Basal and Gpp(NH)p-stimulated adenylate cyclase activity was reduced in DCM but not in ICM. The number of beta-adrenoceptors was similarly reduced both in DCM and ICM compared with NF. Alterations of m-cholinoceptors or A1-adenosine receptors did not occur. Consistently, "indirect" negative inotropic effects of the m-cholinoceptor agonist carbachol and the A1-adenosine receptor agonist R-PIA were not different in ICM, DCM, and nonfailing myocardium. In ICM and DCM, there was a marked reduction of the positive inotropic responses to isoprenaline and milrinone. However, there was a further reduction in DCM compared with ICM. It is concluded that the increase of Gi alpha is accompanied by a reduction of basal and guanine-nucleotide-stimulated adenylate cyclase activity. Alterations of m-cholinoceptors and A1-adenosine receptors do not appear to be involved. The further decrease of the positive inotropic effects of isoprenaline and milrinone in DCM provides evidence that the increase of Gi alpha is functionally relevant in DCM but not ICM and hence might contribute to the reduced effects of endogenous catecholamines and exogenous cAMP-dependent positive inotropic agents in the former but not the latter condition.