Department of Experimental Surgery, McGill University, Montreal, QC H3G 1A4, Canada.
Shriners Hospital for Children, Montreal, QC H4A 0A9, Canada.
Int J Mol Sci. 2021 Mar 27;22(7):3468. doi: 10.3390/ijms22073468.
P2Y13 is an ADP-stimulated G-protein coupled receptor implicated in many physiological processes, including neurotransmission, metabolism, pain, and bone homeostasis. Quantitative understanding of P2Y13 activation dynamics is important for translational studies. We systematically identified PubMed annotated studies that characterized concentration-dependence of P2Y13 responses to natural and synthetic agonists. Since the comparison of the efficacy (maximum response) is difficult for studies performed in different systems, we normalized the data and conducted a meta-analysis of EC (concentration at half-maximum response) and Hill coefficient (slope) of P2Y13-mediated responses to different agonists. For signaling events induced by heterologously expressed P2Y13, EC of ADP-like agonists was 17.2 nM (95% CI: 7.7-38.5), with Hills coefficient of 4.4 (95% CI: 3.3-5.4), while ATP-like agonists had EC of 0.45 μM (95% CI: 0.06-3.15). For functional responses of endogenously expressed P2Y13, EC of ADP-like agonists was 1.76 μM (95% CI: 0.3-10.06). The EC of ADP-like agonists was lower for the brain P2Y13 than the blood P2Y13. ADP-like agonists were also more potent for human P2Y13 compared to rodent P2Y13. Thus, P2Y13 appears to be the most ADP-sensitive receptor characterized to date. The detailed understanding of tissue- and species-related differences in the P2Y13 response to ADP will improve the selectivity and specificity of future pharmacological compounds.
P2Y13 是一种 ADP 刺激的 G 蛋白偶联受体，参与许多生理过程，包括神经递质传递、代谢、疼痛和骨稳态。定量了解 P2Y13 的激活动力学对于转化研究很重要。我们系统地确定了 PubMed 注释研究，这些研究描述了 P2Y13 对天然和合成激动剂的浓度依赖性反应。由于比较不同系统中进行的研究的效价（最大反应）很困难，因此我们对数据进行了归一化，并对 P2Y13 介导的不同激动剂反应的 EC（半最大反应浓度）和 Hill 系数（斜率）进行了荟萃分析。对于异源表达的 P2Y13 诱导的信号事件，ADP 样激动剂的 EC 为 17.2 nM（95%CI：7.7-38.5），Hill 系数为 4.4（95%CI：3.3-5.4），而 ATP 样激动剂的 EC 为 0.45 μM（95%CI：0.06-3.15）。对于内源性表达的 P2Y13 的功能反应，ADP 样激动剂的 EC 为 1.76 μM（95%CI：0.3-10.06）。脑 P2Y13 的 ADP 样激动剂 EC 低于血液 P2Y13。与啮齿动物 P2Y13 相比，ADP 样激动剂对人 P2Y13 的作用更强。因此，P2Y13 似乎是迄今为止特征最明确的最敏感 ADP 的受体。详细了解 P2Y13 对 ADP 的反应在组织和物种之间的差异，将提高未来药理学化合物的选择性和特异性。
