Acquisition by innervated cardiac myocytes of a pertussis toxin-specific regulatory protein linked to the alpha 1-receptor.

Acquisition by innervated cardiac myocytes of a pertussis toxin-specific regulatory protein linked to the alpha 1-receptor.
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受神经支配的心肌细胞获得与 α1 受体相连的百日咳毒素特异性调节蛋白。

DOI:
10.1126/science.2994230
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发表时间:
1985
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Robinson,RB
Robinson,RB
中科院分区:
--
文献类型:
--
作者:
Steinberg,SF;Drugge,ED;Bilezikian,JP;Robinson,RB

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在发育过程中,大鼠心室心肌对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肌细胞的收缩率,但当将肌细胞与功能性交感神经元一起培养时,会降低收缩率。在完整的心室和培养的肌细胞中,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性获得一致。来自交感神经元培养的心肌细胞和成年大鼠心肌的 41 千道尔顿蛋白质显示,与对照相比,百日咳毒素相关的 ADP 核糖基化(ADP,二磷酸腺苷)分别增加了 2.2 倍和 16 倍。在神经肌肉培养物中,通过百日咳毒素特异性 ADP-核糖基化抑制该蛋白质的作用,逆转了成熟的抑制性 α1-肾上腺素能反应对不成熟的刺激模式的反应。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动性的降低相关。
During development, the chronotropic response of rat ventricular myocardium to α1-adrenergic stimulation changes from positive to negative. The α1-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 α1-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 α1-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 α1-adrenergic response becomes linked to a decrease in automaticity.