Opposite effects of α1- and β-adrenoceptor stimulation on both glutamate- and γ-aminobutyric acid-mediated spontaneous transmission in cultured rat hippocampal neurons
Opposite effects of α1- and β-adrenoceptor stimulation on both glutamate- and γ-aminobutyric acid-mediated spontaneous transmission in cultured rat hippocampal neurons
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DOI：
10.1002/jnr.10516
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发表时间：
2003-02-15
影响因子：
4.2
通讯作者：
Vignes, M
中科院分区：
文献类型：
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作者：
Croce, A;Astier, H;Vignes, M
通过记录自发兴奋性和抑制性突触后电流（sEPSC 和 sIPSC），研究刺激肾上腺素能受体对培养的大鼠海马神经元自发突触传递的影响。去甲肾上腺素 (NA) 以浓度依赖性方式抑制 sEPSC，在 10 muM 时效果最大。 α(1)-和α(2)-肾上腺素受体选择性激动剂西拉唑啉和可乐定诱导sEPSC出现的抑制，而β-肾上腺素受体激动剂异丙肾上腺素则引起sEPSC出现的增加。 α(1)-肾上腺素受体阻断可逆转 NA 的抑制作用。进一步研究了γ-氨基丁酸（GABA）（B）受体刺激对NA抑制作用的参与。用巴氯芬刺激 GABA(B) 受体会引起爆发活性的强烈抑制，这种抑制可被 GABA(B) 拮抗剂 CGP 55845 完全逆转。CGP 55845 本身对 sEPSC 频率产生刺激作用。在 CGP 55845 存在的情况下，西拉唑啉和可乐定的抑制作用得以维持。 NA（1、10 和 100 muM）和 α-肾上腺素受体激动剂可减少微型 EPSC 和 IPSC 的发生，而 β-肾上腺素能刺激则可增加其发生。在 50% 的检查细胞中，NA (1, 10 muM) 对 sIPSC 具有刺激作用，而在其余 50% 的细胞中，NA (1, 10 muM) 具有抑制作用。在所有细胞中，100 μM NA 诱导 sIPSC 的抑制。 NA 的抑制作用是由于 α(1) 受体刺激，而兴奋作用是由于 β 受体刺激。在培养的海马神经元中，自发的兴奋性和抑制性突触传递都会受到肾上腺素受体刺激的类似改变。然而，在细胞亚群中，低浓度的 NA 通过 β-肾上腺素受体激活介导 sIPSC 的增加。 (C) 2002 Wiley-Liss, Inc.
The effects of adrenergic receptor stimulation on spontaneous synaptic transmission were investigated in cultured rat hippocampal neurons by recording spontaneous excitatory and inhibitory postsynaptic currents (sEPSC and sIPSC). Noradrenaline (NA) inhibited sEPSC in a concentration-dependent manner, with maximal effect at 10 muM. The alpha(1)- and alpha(2)-adrenoceptor-selective agonists cirazoline and clonidine induced an inhibition of sEPSC appearance, whereas the beta-adrenoceptor agonist isoproterenol elicited an increase. The inhibitory effect of NA was reversed by alpha(1)-adrenoceptor blockade. The participation of gamma-aminobutyric acid (GABA)(B)-receptor stimulation in the inhibitory effect of NA was further examined. GABA(B)-receptor stimulation with baclofen induced a strong inhibition of bursting activity, which was fully reversed by the GABA(B) antagonist CGP 55845. By itself, CGP 55845 exerted a stimulatory effect on sEPSC frequency. In the presence of CGP 55845, the inhibitory effects of cirazoline and clonidine were maintained. NA (1, 10, and 100 muM) and alpha-adrenoceptor agonists decreased miniature EPSC and IPSC occurrence, whereas beta-adrenergic stimulation increased it. In 50% of the cells examined, NA (1, 10 muM) had a stimulatory effect on sIPSC, whereas, in the remaining 50% of cells, NA (1, 10 muM) had an inhibitory effect. In all the cells, 100 muM NA induced an inhibition of sIPSC. The inhibitory effect of NA was due to alpha(1)-receptor stimulation, whereas the excitatory effect was due to beta-receptor stimulation. In cultured hippocampal neurons, spontaneous excitatory and inhibitory synaptic transmissions are both similarly altered by adrenoceptor stimulation. However, in a subset of cells, low concentrations of NA mediate an increase of sIPSC via beta-adrenoceptor activation. (C) 2002 Wiley-Liss, Inc.