Identification and characterization of G protein-coupled nucleotide and nucleotide-like receptors P2Y13 and GPR17

Identification and characterization of G protein-coupled nucleotide and nucleotide-like receptors P2Y13 and GPR17 Purinergic receptors are divided into three subfamilies, P1 (adenosine), P2 (nucleotide) and P0 (adenine) receptors. P2 receptors comprise ligand-gated ion channels - shortly LGICs, receptors P2X1-7, and class A, δ-branch GPCRs termed P2Y1,2,3,6,12-14. The P2Y13 receptor is physiologically activated by ADP and coupled to Gi whose activation results in an inhibition of adenylate cyclase. P2Y13 receptor activation has been reported to be neuroprotective. P2Y13 receptors also play a role in lipoprotein metabolism and cholesterol transport, making the receptor an interesting target for the potential treatment of atherosclerosis. The nucleotide-like orphan receptor GPR17, whose endogenous agonist remains still unknown, is also Gi-coupled. GPR17 appears to be involved in demyelinating diseases such as multiple sclerosis, and some inflammatory diseases. The development of potent, selective ligands, agonists and antagonists, for both P2Y13 and GPR17, is required to study their physiological and pathophysiological roles and for validating the receptors as future drug targets. In the present study, we aim to find out, if the approach via β-arrestin assay employing an enzyme complementation is..