Norepinephrine and isoproterenol increase the phosphorylation of synapsin I and synapsin II in dentate slices of young but not aged Fisher 344 rats.
Norepinephrine and isoproterenol increase the phosphorylation of synapsin I and synapsin II in dentate slices of young but not aged Fisher 344 rats.
复制标题
去甲肾上腺素和异丙肾上腺素会增加年轻而非老年 Fisher 344 大鼠齿状切片中突触蛋白 I 和突触蛋白 II 的磷酸化。
DOI：
10.1073/pnas.88.6.2361
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发表时间：
1991
影响因子：
11.1
通讯作者：
Browning,MD
中科院分区：
文献类型：
--
作者：
Parfitt,KD;Hoffer,BJ;Browning,MD
最近的一些报告表明，去甲肾上腺素（NE）产生一种类似于长期增强（LTP）的突触增强形式。LTP被认为是一种与记忆相关的电生理反应，它在一定程度上涉及到递质释放的增强。虽然NE的作用还没有明确地与LTP联系起来，但很明显，NE可以增加海马齿状回的递质释放。本研究的目的是确定NE是否能够增强synapsin I和synapsin II的磷酸化，这两种同源磷酸化蛋白被认为参与调节神经递质释放。NE （10 μ m）和异丙肾上腺素（250 μ m）使幼鼠齿状切片突触素I和突触素II磷酸化增加。通过有限的蛋白水解对synapsin I进行磷酸化位点分析，表明NE和异丙肾上腺素增加了Ca2+/钙调素依赖性蛋白激酶II和camp依赖性蛋白激酶修饰位点上synapsin I的磷酸化。这些数据表明，NE刺激突触素I在其Ca2+/钙调素依赖性蛋白激酶II位点的磷酸化，该位点已被证明调节突触素I对神经递质释放的影响。我们还研究了NE和异丙肾上腺素对老年动物齿状切片中突触蛋白磷酸化的影响。这些动物先前已被证明表现出NE敏感性的缺陷以及表现LTP能力的显著损伤。在老龄动物切片中，NE和异丙肾上腺素均未刺激突触蛋白磷酸化。有趣的是，突触蛋白磷酸化的基础水平在老年动物的切片中更高。这种较高的基础磷酸化水平可能是老年动物未能表现出ne刺激的突触蛋白磷酸化增加的原因。我们假设β -肾上腺素能激动剂刺激的幼鼠突触素I和突触素II磷酸化在齿状体中NE产生的递质释放增加中起作用。因此，老年大鼠未能表现出这种磷酸化可能是它们未能表现出对NE的正常反应的部分原因。此外，这些突触蛋白磷酸化缺陷也可能在老年大鼠可塑性缺陷中发挥一定作用。
A number of recent reports have suggested that norepinephrine (NE) produces a form of synaptic enhancement that resembles long-term potentiation (LTP). LTP, thought to be an electrophysiological correlate of memory, in part involves an augmentation of transmitter release. Although the effects of NE have not been unequivocally linked to LTP, it is clear that NE can produce increased transmitter release in the dentate gyrus of the hippocampus. The purpose of this study was to determine whether NE was capable of enhancing the phosphorylation of synapsin I and synapsin II, two homologous phosphoproteins thought to be involved in modulation of neurotransmitter release. NE (10 microM) and isoproterenol (250 nM) produced an increase in the phosphorylation of synapsin I and synapsin II in dentate slices from young rats. Phosphorylation site analysis of synapsin I, performed by limited proteolysis, indicated that NE and isoproterenol increased the phosphorylation of synapsin I at sites modified by Ca2+/calmodulin-dependent protein kinase II as well as cAMP-dependent protein kinase. These data demonstrate that NE stimulates the phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II site, which is a site that has been shown to regulate the effect of synapsin I on neurotransmitter release. We have also examined the effects of NE and isoproterenol on synapsin phosphorylation in dentate slices prepared from aged animals. Such animals have previously been shown to exhibit deficits in NE sensitivity as well as significant impairment in their ability to exhibit LTP. Neither NE nor isoproterenol stimulated synapsin phosphorylation in slices prepared from aged animals. Interestingly, the basal level of phosphorylation of the synapsin proteins was higher in slices prepared from aged animals. This higher basal level of phosphorylation may underlie the failure of aged animals to exhibit NE-stimulated increases in phosphorylation of the synapsin proteins. We hypothesize that the beta-adrenergic agonist-stimulated phosphorylation of synapsin I and synapsin II in young rats plays a role in the increase in transmitter release produced by NE in the dentate. Thus, the failure of the aged rats to show such phosphorylation may underlie, in part, their failure to exhibit normal responsiveness to NE. Moreover, these deficits in synapsin phosphorylation may also play some role in the deficits in plasticity seen in aged rats.