Identification and characterization of a cell-surface receptor, P2Y15, for AMP and adenosine
Identification and characterization of a cell-surface receptor, P2Y15, for AMP and adenosine
复制标题
DOI：
10.1074/jbc.m400360200
复制
发表时间：
2004-05-07
影响因子：
4.8
通讯作者：
Encinas, JA
中科院分区：
文献类型：
--
作者：
Inbe, H;Watanabe, S;Encinas, JA
AMP和腺苷存在于所有类型的细胞中，并且可以由细胞释放或由ATP和ADP的分解在细胞外产生。我们已经确定了一个孤儿G蛋白偶联受体与同源的P2 Y家族的核苷酸受体，可以响应AMP和腺苷。基于其功能性结合核苷酸AMP的能力，我们将其命名为P2 Y15。在刺激后，P2 Y15诱导Ca 2+动员和环AMP产生，表明偶联到至少两种不同的G蛋白。它在肥大细胞中高度表达，主要存在于呼吸道和肾脏的组织中，已知这些组织受AMP、腺苷和腺苷拮抗剂的影响。到目前为止，AMP的作用一直被认为取决于其对腺苷的去磷酸化，但我们在这里通过显示P2 Y15结合[P-32] AMP来证明P2 Y15是真正的AMP受体。由于AMP和腺苷具有可被茶碱抑制的支气管收缩作用，我们测试了茶碱和其他腺苷受体拮抗剂是否可以阻断P2 Y15。我们发现在治疗剂量范围内的茶碱浓度下的抑制，表明P2 Y15可能是这种药物的临床重要靶点。
AMP and adenosine are found in all cell types and can be released by cells or created extracellularly from the breakdown of ATP and ADP. We have identified an orphan G protein-coupled receptor with homology to the P2Y family of nucleotide receptors that can respond to both AMP and adenosine. Based on its ability to functionally bind the nucleotide AMP, we have named it P2Y15. Upon stimulation, P2Y15 induces both Ca2+ mobilization and cyclic AMP generation, suggesting coupling to at least two different G proteins. It is highly expressed in mast cells and is found predominantly in the tissues of the respiratory tract and kidneys, which are known to be affected by AMP, adenosine, and adenosine antagonists. Until now, the effects of AMP have been thought to depend on its dephosphorylation to adenosine but we demonstrate here that P2Y15 is a bona fide AMP receptor by showing that it binds [P-32] AMP. Because AMP and adenosine have bronchoconstrictive effects that can be inhibited by theophylline, we tested whether theophylline and other adenosine receptor antagonists can block P2Y15. We found inhibition at a theophylline concentration well within the therapeutic dose range, indicating that P2Y15 may be a clinically important target of this drug.