COMPARISON BETA2 VS BETA1 ADRENOCEPTOR STIMULATION IN RAT CARDIOCYTE STIMULATION

β-肾上腺素能受体(BetaAR)的刺激具有深刻的调制作用 对心脏收缩的影响。已经有很好的证据表明 β1和β2 AR亚型都与腺苷环化酶偶联，并且 他们被β1和β2受体特异性激动剂刺激导致 营地的增加。对其他心脏细胞受体的刺激，例如 前列腺素，也导致cAMP的增加，但对 收缩，大概是因为受影响的营地池没有 与膜上cAMP激活有关，与心脏无关 细胞内钙调节。人们普遍认为，对β的刺激 AR导致微粒(膜结合)cAMP增加 关键蛋白的水平和蛋白激酶(PK)的磷酸化 在兴奋-收缩耦合中。然而，无论Beta2 AR 刺激增加颗粒cAMP和cAMP依赖 磷酸化尚不清楚。在这方面，我们最近已经表明 β_2受体介导的钙、收缩和L型钙的作用 大鼠心肌细胞通道与大鼠心肌细胞通道明显不同 β1受体刺激。在这个项目中，我们进一步证明了 β2对这些细胞内钙离子和收缩的影响不是中介的 通过露营。这一结论是基于对总量和 颗粒物cAMP水平和脱钩之间的增加 CAMP水平升高，细胞收缩增加，CAI一过性。 此外，肌浆网(SR)的磷酸化 β1受体刺激可显著增加磷蛋白的表达，但 而不是通过Beta2AR刺激。因此，Beta1和Beta2AR连接到 细胞内钙动态平衡和收缩的细胞效应 不同的信号转导途径。

Beta-adrenergic receptor (betaAR) stimulation has profound modulatory effects on the cardiac contraction. It has been well documented that both the beta1 and beta2 AR subtypes are coupled to adenylcyclase and that their stimulation by beta1 and beta2 AR specific agonist leads to an increase in cAMP. Stimulation of other heart cell receptors, e.g. prostaglandin, also leads to an increase in cAMP but has no effect on contraction, presumably because the cAMP pool affected is not associated with membranous cAMP activation and is not linked to heart cell Ca2+ regulation. It is widely recognized that stimulation of beta AR's leads to an increase in the particulate (membrane bound) cAMP levels and protein kinase (PK) phosphorylation of key proteins involved in excitation-contraction coupling. However, whether beta2 AR stimulation increases particulate cAMP and cAMP dependent phosphorylation is not known. In this regard we have recently shown that the beta2 AR mediated effects on Ca2+, contraction and L type Ca2+ channels in rat heart cells differ markedly from those elicited by beta1 AR stimulation. In this project we further demonstrated that the beta2 effects on Ca2+ and contraction in these cells are not mediated by cAMP. This conclusion is based on the measurement of total and particulate cAMP levels and the discoupling between the increase of cAMP levels and increases in cell contraction and Cai transient. Furthermore, phosphorylation of sarcoplasmic reticulum (SR) phospholamban was dramatically increased by beta1 AR stimulation, but not by beta2AR stimulation. Thus, beta1 and beta2AR are coupled to cellular effects of altered Ca2+ homeostasis and contraction via different signal transduction pathways.