P2Y receptors are
G-protein-coupled receptors (GPCRs) for extracellular
nucleotides. There are eight mammalian P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14). P2Y receptors are widely expressed and play important roles in physiology and pathophysiology. One important example is the
ADP-induced platelet aggregation mediated by P2Y1 and P2Y12 receptors. Active metabolites of the
thienopyridine compounds
ticlopidine,
clopidogrel and
prasugrel as well as the
nucleoside analogue
ticagrelor block P2Y12 receptors and thereby platelet aggregation. These drugs are used for the prevention and
therapy of cardiovascular events. Moreover, P2Y receptors play important roles in the nervous system.
Adenine nucleotides modulate neuronal activity and neuronal fibre outgrowth by activation of
P2Y1 receptors and control migration of microglia by P2Y12 receptors.
UDP stimulates microglial phagocytosis through activation of
P2Y6 receptors. There is evidence for a role for
P2Y2 receptors in
Alzheimer's disease pathology. The P2Y receptor subtypes are highly diverse in both their amino acid sequences and their pharmacological profiles. Selective receptor
ligands have been developed for the pharmacological characterization of the receptor subtypes. The recently published three-dimensional crystal structures of the human P2Y1 and P2Y12 receptors will facilitate the development of therapeutic agents that selectively target P2Y receptors. This article is part of the Special Issue entitled '
Purines in Neurodegeneration and Neuroregeneration'.