Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission
Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission
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DOI：
10.1038/46040
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发表时间：
1999-11-11
期刊：
影响因子：
64.8
通讯作者：
Kobilka, BK
中科院分区：
文献类型：
--
作者：
Hein, L;Altman, JD;Kobilka, BK
交感神经系统通过激活心脏、血管和肾脏中的肾上腺素能受体来调节心血管功能（1），已知α（2）-肾上腺素能受体在调节来自交感神经和来自中枢神经系统中的肾上腺素能神经元的神经递质释放中具有关键作用（2-5）;然而，三种高度同源的α（2）-肾上腺素能受体亚型（α（2A）、α（2B）、α（2C））在该过程中的各自作用尚不清楚。我们现在已经研究了编码三种α（z）肾上腺素能受体亚型的基因被破坏的小鼠的神经递质释放。在这里，我们表明，α（2A）-和α（2C）-亚型是所需的正常突触前控制的心脏交感神经和中枢去甲肾上腺素能神经元的递质释放。α（2A）-肾上腺素能受体在高刺激频率下抑制递质释放，而α，c-亚型在较低水平的神经活动下调节神经传递。低频和高频调节似乎在生理学上都很重要，因为缺乏α（2A）和α（2C）受体亚型的小鼠血浆去甲肾上腺素浓度升高，并在4个月龄时发生心脏肥大伴左心室收缩力降低。
The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney(1), alpha(2)-Adrenergic receptors are known to have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system(2-5); however, the individual roles of the three highly homologous alpha(2)-adrenergic-receptor subtypes (alpha(2A), alpha(2B), alpha(2C)) in this process are not known. We have now studied neurotransmitter release in mice in which the genes encoding the three alpha(z)-adrenergic-receptor subtypes were disrupted. Here we show that both the alpha(2A)- and alpha(2C)-subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. alpha(2A)-Adrenergic receptors inhibit transmitter release at high stimulation frequencies, whereas the a,c-subtype modulates neurotransmission at lower levels of nerve activity. Both low- and high-frequency regulation seem to be physiologically important, as mice lacking both alpha(2A)- and alpha(2C)-receptor subtypes have elevated plasma noradrenaline concentrations and develop cardiac hypertrophy with decreased left ventricular contractility by four months of age.