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首页> 外文期刊>The European Journal of Neuroscience >Co-localization and functional cross-talk between A1 and P2Y1 purine receptors in rat hippocampus.
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Co-localization and functional cross-talk between A1 and P2Y1 purine receptors in rat hippocampus.

机译：大鼠海马中A1和P2Y1嘌呤受体之间的共定位和功能性串扰。

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摘要

Adenosine and ATP, via their specific P1 and P2 receptors, modulate a wide variety of cellular and tissue functions, playing a neuroprotective or neurodegenerative role in brain damage conditions. Although, in general, adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, recent data suggest the existence of a heterodimerization and a functional interaction between P1 and P2 receptors in the brain. In particular, interactions of adenosine A1 and P2Y1 receptors may play important roles in the purinergic signalling cascade. In the present work, we investigated the subcellular localization/co-localization of the receptors and their functional cross-talk at the membrane level in Wistar rat hippocampus. This is a particularly vulnerable brain area, which is sensitive to adenosine- and ATP-mediated control of glutamatergic transmission. The postembedding immunogold electron microscopy technique showed that the two receptors are co-localized at the synaptic membranes and surrounding astroglial membranes of glutamatergic synapses. To investigate the functional cross-talk between the two types of purinergic receptors, we evaluated the reciprocal effects of their activation on their G protein coupling. P2Y1 receptor stimulation impaired the potency of A1 receptor coupling to G protein, whereas the stimulation of A1 receptors increased the functional responsiveness of P2Y1 receptors. The results demonstrated an A1-P2Y1 receptor co-localization at glutamatergic synapses and surrounding astrocytes and a functional interaction between these receptors in hippocampus, suggesting ATP and adenosine can interact in purine-mediated signalling. This may be particularly important during pathological conditions, when large amounts of these mediators are released.
机译：腺苷和ATP通过其特定的P1和P2受体，调节多种细胞和组织功能，在脑损伤情况下发挥神经保护或神经退行性作用。尽管通常腺苷会抑制兴奋性，而ATP在中枢神经系统中起兴奋性递质的作用，但最近的数据表明大脑中存在异二聚化作用以及P1和P2受体之间的功能相互作用。特别是，腺嘌呤A1和P2Y1受体的相互作用可能在嘌呤能信号级联反应中起重要作用。在目前的工作中，我们调查了Wistar大鼠海马中受体的亚细胞定位/共定位及其在膜水平的功能性串扰。这是一个特别脆弱的大脑区域，对腺苷和ATP介导的谷氨酸能传递控制敏感。包埋后免疫金电子显微镜技术表明，这两个受体共定位于谷氨酸能突触的突触膜和周围的星形胶质膜。为了研究两种嘌呤能受体之间的功能性相互作用，我们评估了它们的活化对其G蛋白偶联的相互影响。 P2Y1受体刺激削弱了A1受体与G蛋白偶联的能力，而A1受体的刺激增加了P2Y1受体的功能反应性。结果表明，A1-P2Y1受体在谷氨酸能突触和周围星形胶质细胞中共定位，并且这些受体在海马体中发生功能性相互作用，表明ATP和腺苷可以在嘌呤介导的信号传导中相互作用。当大量的这些介质被释放时，这在病理状态下可能尤其重要。

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