Novotny J, Kvapil P, Jelinek F, Ransnäs L A
Wallenberg Laboratory for Cardiovascular Research, Gothenburg University, Sweden.
Cardiovasc Res. 1995 Oct;30(4):602-10.
Cardiomyopathy is usually associated with marked alterations in myocardial transmembrane signalling. Although acute viral myocarditis may result in chronic cardiomyopathy in some cases, the possible consequences of viral infection on function of the myocardial signal-transducing complex have not been explored. Therefore, the present study was designed to investigate the G-protein-regulated adenylyl cyclase signalling system in murine myocardium during myocarditis induced by coxsackievirus B3 (CVB3) infection.
We examined the functional characteristics of adenylyl cyclase as well as the function and distribution of beta-adrenoceptors, m-cholinoceptors and G-proteins in myocardial plasma membranes isolated from the hearts of mice with acute (7 days pi) or late phase (21 days pi) myocarditis and the obtained results were compared with the corresponding data determined in age-matched controls.
While the basal adenylyl cyclase activity was not significantly altered, the ability of forskolin, sodium fluoride and GTP gamma S to activate adenylyl cyclase was lowered by about 20% in samples from virus-infected animals. The level of Gs alpha in myocardial plasma membranes as well as the functional activity of Gs alpha was not affected by viral infection, but the Gi alpha content was increased by about 20%. The total number of beta-adrenoceptors in myocardial plasma membranes increased by about 12-15% due to higher content of the beta 2-adrenoceptor subtype. Although the agonist-binding parameters of beta-adrenoceptors were not significantly altered, the ability of these receptors to mediate stimulation of adenylate cyclase was markedly diminished (by 56-80%). The total number of m-cholinoceptors in samples derived from virus-infected mice increased considerably (by 29-59%) and a significant proportion of the receptors shifted to a higher affinity status, but their ability to transduce agonist signals was impaired.
These data are the first to demonstrate that several different sites of the myocardial G-protein-regulated adenylyl cyclase signalling complex are significantly altered in acute as well as in late phase of CVB3-induced myocarditis.
心肌病通常与心肌跨膜信号的显著改变有关。虽然急性病毒性心肌炎在某些情况下可能导致慢性心肌病，但病毒感染对心肌信号转导复合物功能的潜在影响尚未得到研究。因此，本研究旨在调查柯萨奇病毒B3（CVB3）感染诱导的心肌炎期间小鼠心肌中G蛋白调节的腺苷酸环化酶信号系统。
我们检测了腺苷酸环化酶的功能特性以及急性（感染后7天）或晚期（感染后21天）心肌炎小鼠心脏分离的心肌质膜中β-肾上腺素能受体、M胆碱能受体和G蛋白的功能及分布，并将所得结果与年龄匹配的对照组中测定的相应数据进行比较。
虽然基础腺苷酸环化酶活性没有显著改变，但在病毒感染动物的样本中，福斯可林、氟化钠和GTPγS激活腺苷酸环化酶的能力降低了约20%。心肌质膜中Gsα的水平及其功能活性不受病毒感染的影响，但Giα含量增加了约20%。由于β2-肾上腺素能受体亚型含量较高，心肌质膜中β-肾上腺素能受体的总数增加了约12-15%。虽然β-肾上腺素能受体的激动剂结合参数没有显著改变，但这些受体介导腺苷酸环化酶刺激的能力明显减弱（降低了56-80%）。病毒感染小鼠样本中M胆碱能受体的总数显著增加（增加了29-59%），且相当一部分受体转变为高亲和力状态，但其转导激动剂信号的能力受损。
这些数据首次表明，在CVB3诱导的心肌炎的急性期和晚期，心肌G蛋白调节腺苷酸环化酶信号复合物的几个不同位点发生了显著改变。
