TY - JOUR
T1 - Update of P2Y receptor pharmacology
T2 - IUPHAR Review 27
AU - Jacobson, Kenneth A.
AU - Delicado, Esmerilda G.
AU - Gachet, Christian
AU - Kennedy, Charles
AU - von Kügelgen, Ivar
AU - Li, Beibei
AU - Miras-Portugal, M. Teresa
AU - Novak, Ivana
AU - Schöneberg, Torsten
AU - Perez-Sen, Raquel
AU - Thor, Doreen
AU - Wu, Beili
AU - Yang, Zhenlin
AU - Müller, Christa E.
PY - 2020/2/9
Y1 - 2020/2/9
N2 - Eight G protein-coupled P2Y receptor subtypes respond to extracellular adenine and uracil mononucleotides and dinucleotides. P2Y receptors belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies: P2Y
1, P2Y
2, P2Y
4, P2Y
6, and P2Y
11 (principally G
q protein-coupled P2Y
1-like) and P2Y
12–14 (principally G
i protein-coupled P2Y
12-like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y
1, P2Y
2, P2Y
4, and P2Y
6 receptors induce vasodilation, while smooth muscle P2Y
2, P2Y
4, and P2Y
6 receptor activation leads to vasoconstriction. Pancreatic P2Y
1 and P2Y
6 receptors stimulate while P2Y
13 receptors inhibits insulin secretion. Antagonists of P2Y
12 receptors, and potentially P2Y
1 receptors, are anti-thrombotic agents, and a P2Y
2/P2Y
4 receptor agonist treats dry eye syndrome in Asia. P2Y receptor agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2Y receptor pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modelling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting.
AB - Eight G protein-coupled P2Y receptor subtypes respond to extracellular adenine and uracil mononucleotides and dinucleotides. P2Y receptors belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies: P2Y
1, P2Y
2, P2Y
4, P2Y
6, and P2Y
11 (principally G
q protein-coupled P2Y
1-like) and P2Y
12–14 (principally G
i protein-coupled P2Y
12-like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y
1, P2Y
2, P2Y
4, and P2Y
6 receptors induce vasodilation, while smooth muscle P2Y
2, P2Y
4, and P2Y
6 receptor activation leads to vasoconstriction. Pancreatic P2Y
1 and P2Y
6 receptors stimulate while P2Y
13 receptors inhibits insulin secretion. Antagonists of P2Y
12 receptors, and potentially P2Y
1 receptors, are anti-thrombotic agents, and a P2Y
2/P2Y
4 receptor agonist treats dry eye syndrome in Asia. P2Y receptor agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2Y receptor pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modelling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting.
KW - GPCR
KW - G protein-coupled receptor
KW - nucleotide receptors
KW - P2Y receptors
KW - nucleotides
U2 - 10.1111/bph.15005
DO - 10.1111/bph.15005
M3 - Literature review
VL - 177
SP - 2413
EP - 2433
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 11
ER -