Richardson P J, Brown S J, Bailyes E M, Luzio J P
Nature. 1987;327(6119):232-4. doi: 10.1038/327232a0.
One of the most important inhibitory modulators of synaptic transmission in mammalian brain is adenosine. At some cholinergic terminals, adenosine is known to inhibit further release of acetylcholine. It is unclear whether adenosine is released directly at the synapse or whether ATP is co-released with transmitter and hydrolysed to adenosine in the synaptic cleft. Methods used in the past for isolating nerve terminals have not yielded homogeneous preparations, making it impossible to determine whether sufficient ATP or adenosine is released at specific synapses for inhibition of transmitter release to occur. Immunoaffinity purification techniques have recently permitted the preparation of homogeneous populations of cholinergic nerve terminals, which release ATP upon stimulation. We now report that in immunoisolated cholinergic nerve terminals from the striatum synaptic ectophosphohydrolases convert this ATP to adenosine, which inhibits further acetylcholine release, but this inhibitory effect is not seen in cortical cholinergic terminals lacking the complete ectophosphohydrolase pathway. Therefore the differing adenosine-mediated modulation in different brain areas is controlled by the presence and activity of synaptic ectophosphohydrolases.
腺苷是哺乳动物大脑中突触传递最重要的抑制性调节剂之一。在一些胆碱能终末，已知腺苷会抑制乙酰胆碱的进一步释放。目前尚不清楚腺苷是直接在突触处释放，还是ATP与神经递质共同释放并在突触间隙水解为腺苷。过去用于分离神经终末的方法未能得到均一的制剂，因此无法确定在特定突触处是否释放了足够的ATP或腺苷来抑制神经递质的释放。免疫亲和纯化技术最近使得制备均一的胆碱能神经终末群体成为可能，这些终末在受到刺激时会释放ATP。我们现在报告，在来自纹状体的免疫分离胆碱能神经终末中，突触外磷酸水解酶将这种ATP转化为腺苷，后者抑制乙酰胆碱的进一步释放，但在缺乏完整外磷酸水解酶途径的皮质胆碱能终末中未观察到这种抑制作用。因此，不同脑区中腺苷介导的不同调节作用受突触外磷酸水解酶的存在和活性控制。
