Altered signal transduction in cardiac ventricle overexpressing A(1)-adenosine receptors.
Altered signal transduction in cardiac ventricle overexpressing A(1)-adenosine receptors.
复制标题
过度表达 A(1)-腺苷受体的心室信号转导发生改变。
DOI：
10.1016/j.cardiores.2003.09.012
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发表时间：
2003
影响因子：
10.8
通讯作者：
Schmitz,Wilhelm
中科院分区：
文献类型：
--
作者：
Neumann,Joachim;Boknik,Peter;Begrow,Frank;Hanske,Gabriela;Justus,Isabel;Mát'us,Marek;Reinke,Uta;Matherne,GPaul;Schmitz,Wilhelm
Objective:The aim of the present study was to assess the effects of A1-adenosine receptor (A1-AR) stimulation in ventricle of A1-adenosine receptor overexpressing mice (transgenic mice, TG).Methods:Effects of the A1-adenosine receptor agonist R-PIA ((−)-N6-phenylisopropyladenosine) on phosphorylation of phospholamban (PLB), Ca2+transients, Ca2+currents and cell shortening were studied in isolated ventricular cardiomyocytes.Results:R-PIA alone did not affect contractility in isolated electrically stimulated cardiomyocytes from wild-type mice (WT) or TG. However, after pre-stimulation of β-adrenoceptors by isoproterenol, R-PIA reduced contractility in cardiomyocytes from WT but increased contractility in TG. Under the same conditions, R-PIA reduced isoproterenol-stimulated currents through L-type Ca2+channels, Ca2+transients and phosphorylation of PLB in cardiomyocytes from WT. In contrast, R-PIA diminished phospholamban phosphorylation induced by isoproterenol but augmented isoproterenol-elevated currents through L-type Ca2+channels, and isoproterenol-heightened Ca2+transients in cardiomyocytes from TG.Conclusions:We suggest that A1-adenosine receptor overexpression reverses the interaction of β-adrenergic and A1-adenosine receptor stimulation, at least in part. Hence, the receptor/effector coupling is dependent on receptor density in this model.
