Communi D, Motte S, Boeynaems J M, Pirotton S
Institute of Interdisciplinary Research, School of Medicine, Erasme Hospital, Université Libre de Bruxelles, Belgium.
Eur J Pharmacol. 1996 Dec 19;317(2-3):383-9. doi: 10.1016/s0014-2999(96)00740-6.
The P2Y4 receptor is a new member of the P2Y family which functionally behaves as a pyrimidinergic receptor. The pharmacological properties of the human P2Y4 receptor have been characterized following its stable expression in 1321N1 astrocytoma cells. UTP induced a biphasic accumulation of inositol trisphosphates, with an early peak at 30 s followed by a smaller but more sustained accumulation. ATP was a pure antagonist at early times and later behaved as a partial agonist. At 20 min, the rank order of potency of various nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP. Diadenosine polyphosphates also stimulated the production of inositol trisphosphates (after 20 min), more potently than ATP, but their maximal effect represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited strongly the UTP response, whereas suramin was inactive and reactive blue 2 had an intermediate effect. Pertussis toxin inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4 receptor can exist in two distinct activation states differing in terms of time-course, specificity for uridine nucleotides and G-protein coupling.
P2Y4受体是P2Y家族的新成员，其功能上表现为嘧啶能受体。人P2Y4受体在1321N1星形细胞瘤细胞中稳定表达后，其药理学特性已得到表征。UTP诱导肌醇三磷酸呈双相积累，30秒时出现早期峰值，随后积累量较小但更持久。ATP在早期是纯拮抗剂，后来表现为部分激动剂。在20分钟时，各种核苷酸的效力排序如下：UTP>UDP =脱氧UTP>5-溴-UTP>ITP>ATP。二腺苷多磷酸也刺激肌醇三磷酸的产生（20分钟后），比ATP更有效，但它们的最大效应仅为UTP的20-25%。磷酸吡哆醛-6-偶氮苯基-2'，4'-二磺酸强烈抑制UTP反应，而苏拉明无活性，活性蓝2有中等作用。百日咳毒素在早期抑制对UTP的反应（30秒时抑制62±5%），但在5或20分钟时不再观察到其作用。据推测，P2Y4受体可以以两种不同的激活状态存在，在时间进程、对尿苷核苷酸的特异性和G蛋白偶联方面有所不同。
