Steinberg S F, Drugge E D, Bilezikian J P, Robinson R B
Science. 1985 Oct 11;230(4722):186-8. doi: 10.1126/science.2994230.
During development, the chronotropic response of rat ventricular myocardium to alpha 1-adrenergic stimulation changes from positive to negative. The alpha 1-agonist phenylephrine increases the rate of contraction of neonatal rat myocytes cultured alone but decreases the rate of contraction when the myocytes are cultured with functional sympathetic neurons. The developmental induction of the inhibitory myocardial response to alpha 1-adrenergic stimulation in intact ventricle and in cultured myocytes was shown to coincide with the functional acquisition of a substrate for pertussis toxin. A 41-kilodalton protein from myocytes cultured with sympathetic neurons and from adult rat myocardium showed, respectively, 2.2- and 16-fold increases in pertussis toxin-associated ADP-ribosylation (ADP, adenosine diphosphate) as compared to controls. In nerve-muscle cultures, inhibition of the actions of this protein by pertussis toxin-specific ADP-ribosylation reversed the mature inhibitory alpha 1-adrenergic response to an immature stimulatory pattern. The results suggest that innervation is associated with the appearance of a functional pertussis toxin substrate by which the alpha 1-adrenergic response becomes linked to a decrease in automaticity.
在发育过程中，大鼠心室肌对α1-肾上腺素能刺激的变时反应从正向变为负向。α1-激动剂去氧肾上腺素可增加单独培养的新生大鼠心肌细胞的收缩速率，但当心肌细胞与功能性交感神经元共同培养时，其收缩速率会降低。完整心室和培养心肌细胞中对α1-肾上腺素能刺激的抑制性心肌反应的发育诱导与百日咳毒素底物的功能获得相一致。与对照组相比，来自与交感神经元共同培养的心肌细胞和成年大鼠心肌的一种41千道尔顿的蛋白质分别显示出与百日咳毒素相关的ADP-核糖基化（ADP，腺苷二磷酸）增加2.2倍和16倍。在神经肌肉培养物中，百日咳毒素特异性ADP-核糖基化对该蛋白质作用的抑制将成熟的抑制性α1-肾上腺素能反应逆转至未成熟的刺激性模式。结果表明，神经支配与功能性百日咳毒素底物的出现有关，通过该底物α1-肾上腺素能反应与自律性降低相关联。
