BETA(2)-ADRENERGIC RECEPTOR ACTIONS IN NEONATAL AND ADULT-RAT VENTRICULAR MYOCYTES
BETA(2)-ADRENERGIC RECEPTOR ACTIONS IN NEONATAL AND ADULT-RAT VENTRICULAR MYOCYTES
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DOI：
10.1161/01.res.76.1.40
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发表时间：
1995-01-01
影响因子：
20.1
通讯作者：
STEINBERG, SF
中科院分区：
文献类型：
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作者：
KUZNETSOV, V;PAK, E;STEINBERG, SF
β(2)-肾上腺素能受体在新生儿和成人心脏中的生理功能尚不完全清楚，也没有考虑到β(2)-受体作用的可能年龄差异。我们使用异丙肾上腺素(混合β(1)和β(2)受体激动剂)和zinterol(β(2)选择性激动剂)来比较新生和成年大鼠心室肌细胞中β受体亚型的作用。当以10(-7)mol/L的终浓度团注给药时，异丙肾上腺素和津特罗均可增加和加速新生心肌细胞钙和细胞缩短瞬变的幅度和动力学。在相同的实验条件下，异丙肾上腺素增加成年心肌细胞钙瞬变和收缩的幅度，并加速其动力学，而津替洛尔则无此作用。在CGP 20712A(β(1)受体阻断剂)存在下，100倍浓度的zinterol使成人心肌细胞的收缩幅度增加，但持续时间延长。为了探索这种年龄依赖的β(2)受体反应性差异的机制，我们比较了新生儿和成人心肌细胞中β受体的表达和对cAMP积累的刺激。新生儿心肌细胞的β受体密度为每细胞186346+/-13356个，成年心肌细胞为186346+/-13356个；β(2)受体的相对比例相近(分别为16.7+/-2.3%和16.9+/-0.9%)。异丙肾上腺素可显著增加新生和成人心肌细胞内cAMP的积聚(分别为基础心肌细胞的20.0+/-1.0和20.6+/-2.6倍)。相比之下，zinterol显著增加了新生心肌细胞中cAMP的积聚，但在成年心肌细胞中仅有轻微增加。这些研究证明，在低浓度的激动剂浓度下，β(2)受体的激活通过增加cAMP，增加幅度和加速成年心肌细胞的收缩动力学来促进正性变力反应。此外，这些结果表明，β(2)受体与信号级联中更远端元件的偶联与年龄相关的差异可以影响心肌细胞β(2)受体的反应性。
The physiological function of beta(2)-adrenergic receptors in the neonatal and adult heart is incompletely understood, and possible age-dependent differences in beta(2)-receptor actions have not been considered. We used isoproterenol (mixed beta(1)- and beta(2)-receptor agonist) and zinterol (beta(2)-selective agonist) to compare beta-receptor subtype actions in neonatal and adult rat ventricular myocytes. When delivered as a bolus at a final concentration of 10(-7) mol/L, both isoproterenol and zinterol increased the amplitude and hastened the kinetics of the calcium and cell-shortening transients in neonatal myocytes. Under identical experimental conditions, isoproterenol increased the amplitude and accelerated the kinetics of the calcium transient and the twitch in adult myocytes, whereas zinterol did not. In the presence of CGP 20712A (beta(1)-receptor blocker), a 100-fold higher concentration of zinterol increased the amplitude but prolonged the duration of the twitch in adult myocytes. To probe the mechanism for this age-dependent difference in beta(2)-receptor responsiveness, we compared beta-receptor expression and stimulation of cAMP accumulation in neonatal and adult myocytes. beta-Receptor density was per cell in neonatal myocytes and 186 346+/-13 356 sites per cell in adult myocytes; the relative proportion of beta(2)-receptors was comparable in each (16.7+/-2.3% and 16.9+/-0.9%, respectively). Isoproterenol induced a large increase in cAMP accumulation in neonatal and adult myocytes (20.0+/-1.0- and 20.6+/-2.6-fold over basal). In contrast, zinterol evoked a substantial increase in cAMP accumulation in neonatal myocytes but only a minor increase in adult myocytes. These studies provide evidence that at low agonist concentrations, beta(2)-receptor activation contributes to the positive inotropic response by increasing cAMP and increasing the amplitude and hastening the kinetics of the twitch in neonatal, but not adult, myocytes. Moreover, these results suggest that age-dependent differences in beta(2)-receptor coupling to more distal elements in the signaling cascade can influence myocyte beta(2)-receptor responsiveness.