Characterization of Potency of the P2Y13 Receptor Agonists: A Meta-Analysis.

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.