Steinberg S F, Rosen T S, Malfatto G, Rosen M R
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
J Mol Cell Cardiol. 1991 Feb;23 Suppl 1:47-52. doi: 10.1016/0022-2828(91)90023-f.
We previously have shown that treatment of neonatal rats (days 1-10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies alpha-adrenergic receptor-effector coupling, such that innervated hearts at day 10 show high levels of a 41 kDa GTP regulatory protein (G protein) that is a substrate for pertussis toxin and that links the alpha 1-receptor to the Na/K pump. This receptor-effector pathway results in alpha adrenergic-induced decreases in automaticity. In contrast, non-innervated hearts at day 10 show lower levels of the pertussis toxin sensitive G-protein and increases in automaticity induced by alpha-agonist. We now report the effects of administration of NGF, Ab or placebo on beta-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1-10 of life. On day 10, the beta-receptor number and affinity and the stimulatory G-protein, Gs, were equivalent across groups. Moreover, the ventricular automatic response to beta-adrenergic receptor stimulation was equivalent across groups suggesting there was no change in receptor-effector coupling as a result of the difference in innervation. These results on beta-adrenergic receptor-effector coupling considered in light of our prior studies on alpha-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of alpha than beta adrenergic modulation of ventricular rhythm.
我们先前已经表明，用神经生长因子（NGF）或其抗体（Ab）处理新生大鼠（出生后1 - 10天）会改变α-肾上腺素能受体与效应器的偶联，使得出生后第10天有神经支配的心脏显示出高水平的一种41 kDa的GTP调节蛋白（G蛋白），该蛋白是百日咳毒素的作用底物，并且将α1-受体与钠钾泵相连接。这种受体-效应器途径导致α-肾上腺素能诱导的自律性降低。相反，出生后第10天无神经支配的心脏显示出较低水平的对百日咳毒素敏感的G蛋白，并且α-激动剂诱导的自律性增加。我们现在报告给予NGF、Ab或安慰剂对新生大鼠β-肾上腺素能受体-效应器偶联的影响。在出生后1 - 10天给大鼠给予NGF、Ab或安慰剂。在第10天，各组之间的β-受体数量、亲和力以及刺激性G蛋白Gs相当。此外，各组对β-肾上腺素能受体刺激的心室自动反应相当，这表明由于神经支配的差异，受体-效应器偶联没有变化。根据我们先前关于α-肾上腺素能偶联的研究来考虑这些关于β-肾上腺素能受体-效应器偶联的结果表明，交感神经支配的发育更多地是心室节律α-肾上腺素能调节而非β-肾上腺素能调节的决定因素。
