Köles Laszlo, Leichsenring Anna, Rubini Patrizia, Illes Peter
Rudolph-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Germany.
Adv Pharmacol. 2011;61:441-93. doi: 10.1016/B978-0-12-385526-8.00014-X.
Purine and pyrimidine nucleotides are extracellular signaling molecules in the central nervous system (CNS) leaving the intracellular space of various CNS cell types via nonexocytotic mechanisms. In addition, ATP is a neuro-and gliotransmitter released by exocytosis from neurons and neuroglia. These nucleotides activate P2 receptors of the P2X (ligand-gated cationic channels) and P2Y (G protein-coupled receptors) types. In mammalians, seven P2X and eight P2Y receptor subunits occur; three P2X subtypes form homomeric or heteromeric P2X receptors. P2Y subtypes may also hetero-oligomerize with each other as well as with other G protein-coupled receptors. P2X receptors are able to physically associate with various types of ligand-gated ion channels and thereby to interact with them. The P2 receptor homomers or heteromers exhibit specific sensitivities against pharmacological ligands and have preferential functional roles. They may be situated at both presynaptic (nerve terminals) and postsynaptic (somatodendritic) sites of neurons, where they modulate either transmitter release or the postsynaptic sensitivity to neurotransmitters. P2 receptors exist at neuroglia (e.g., astrocytes, oligodendrocytes) and microglia in the CNS. The neuroglial P2 receptors subserve the neuron-glia cross talk especially via their end-feets projecting to neighboring synapses. In addition, glial networks are able to communicate through coordinated oscillations of their intracellular Ca(2+) over considerable distances. P2 receptors are involved in the physiological regulation of CNS functions as well as in its pathophysiological dysregulation. Normal (motivation, reward, embryonic and postnatal development, neuroregeneration) and abnormal regulatory mechanisms (pain, neuroinflammation, neurodegeneration, epilepsy) are important examples for the significance of P2 receptor-mediated/modulated processes.
嘌呤和嘧啶核苷酸是中枢神经系统（CNS）中的细胞外信号分子，通过非胞吐机制离开各种CNS细胞类型的细胞内空间。此外，ATP是一种通过神经元和神经胶质细胞的胞吐作用释放的神经递质和胶质递质。这些核苷酸激活P2X（配体门控阳离子通道）和P2Y（G蛋白偶联受体）类型的P2受体。在哺乳动物中，存在7种P2X和8种P2Y受体亚基；3种P2X亚型形成同聚体或异聚体P2X受体。P2Y亚型也可能彼此以及与其他G蛋白偶联受体形成异源寡聚体。P2X受体能够与各种类型的配体门控离子通道发生物理关联，从而与它们相互作用。P2受体同聚体或异聚体对药理配体表现出特定的敏感性，并具有优先的功能作用。它们可能位于神经元的突触前（神经末梢）和突触后（体树突）部位，在那里它们调节递质释放或对神经递质的突触后敏感性。P2受体存在于中枢神经系统的神经胶质细胞（如星形胶质细胞、少突胶质细胞）和小胶质细胞中。神经胶质P2受体尤其通过其伸向相邻突触的终足来实现神经元与胶质细胞的相互作用。此外，胶质细胞网络能够通过其细胞内Ca(2+)在相当长距离上的协调振荡进行通信。P2受体参与中枢神经系统功能的生理调节及其病理生理失调。正常的（动机、奖赏、胚胎和出生后发育、神经再生）和异常的调节机制（疼痛、神经炎症、神经退行性变、癫痫）是P2受体介导/调节过程重要性的重要例子。
