Ralevic V, Burnstock G
University College, London, UK.
Circulation. 1991 Jul;84(1):1-14. doi: 10.1161/01.cir.84.1.1.
Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.
P2嘌呤受体亚型的特性有助于理解嘌呤核苷酸产生的多种不同效应。P2X嘌呤受体位于血管平滑肌上，在那里它们介导由三磷酸腺苷（ATP）作为与去甲肾上腺素一起从交感神经释放的共递质而导致的血管收缩。P2Y嘌呤受体通常位于血管内皮上，在那里它们通过局部产生的ATP作为血管舒张的介质发挥作用。在一些血管中，P2Y嘌呤受体也位于平滑肌上，可能与嘌呤能或感觉神经有关，在那里它们可以引发对神经元释放的ATP的直接舒张作用。ATP及其类似物对离体血管或血管床的净效应将是由P2X和P2Y嘌呤受体亚型介导的作用的结果，尽管血管张力以及神经和内皮细胞完整性的变化可能会改变反应的平衡。在疾病状态（如动脉粥样硬化）中已观察到此类变化，并且可能对P2嘌呤受体参与例如血管痉挛等情况具有重要意义。到目前为止，针对P2X和P2Y嘌呤受体的选择性强效拮抗剂的开发仍然难以实现，其治疗潜力只能进行推测。
