P2Y2 receptor (previously known as P2U, P2U purinoceptor 1, and P2Y purinoceptor 2) 2.1:NUCT:2:P2Y2.
| TM | aa | AC | Chr. Map | References | |
|---|---|---|---|---|---|
| Human* | 7 | 377 | NM_176072; NM_002564; NM_176071 | 11q13.5—q14.1 | Parr et al. (1994) |
| Rat | 7 | 374 | NM_017255 | 1q32 | Chen et al. (1996) |
| Mouse | 7 | 373 | NM_008773 | 7 | Lustig et al. (1993) |
| Functional assays | Rat coronary artery (Godecke et al., 1996); rat salivary glands (Turner et al 1997); human airway epithelium (Clarke et al., 1992); murine gallbladder epithelium (Clarke et al., 1999); current measurement in microinjected rat superior cervical sympathetic neurons (Brown, 2000); calcium imaging in HT29 and Colo320 DM colorectal carcinoma cells (Burnstock and Knight, 2004); HeLa cells (Muscella, 2003); A6 cells (Burnstock and Knight, 2004); HEK 293 cells (Schacter et al., 1996); studies of IP3 accumulation and intracellular calcium mobilization in 1321N1 astrocytoma cells (Parr et al., 1994; Lazarowski et al., 1995a); [3H]inositol polyphosphate metabolism in rat aortic smooth muscle cells (Kumari, 2003); human coronary artery endothelial cells (Seye, 2003); intracellular calcium signaling, electrophysiology, and fluid transport in human fetal, rat, and rabbit retina (Meyer, 2002); Ca2+ mobilization in HL-60 human neutrophil cell line (Meshki, 2004) | ||||
| Ligand | Action | Selectivity | Endogenous | References |
|---|---|---|---|---|
| UTP | Agonist | No | Yes | Lazarowski et al. (1995b) |
| UTPγS | Agonist | No | No | Lazarowski et al. (1995b) |
| ATP | Agonist | No | Yes | Lazarowski et al. (1995b) |
| 5BrUTP | Agonist | No | No | Lazarowski et al. (1995b) |
| 2C1ATP | Agonist | No | No | Lazarowski et al. (1995b) |
| dCp4U (INS37217) | Agonist | No | No | Kellerman et al. (2002) |
| Up4U (INS365) | Agonist | No | No | Pendergast, et al. (2001) |
| Agonist potencies | IP3: UTP (EC50 0.14 ± 0.02 μM) > ATP (EC50 0.23 ± 0.01 μM) > Ap4A (EC50 0.72 ± 0.02 μM) > ATPγS (EC50 1.72 ± 0.15 μM) > 5BrUTP (EC50 2.06 ± 0.04 μM); Ca2+: dCp4U (INS37217) (EC50 0.22 μM); Up4U (INS365) (EC50 0,1 μM) (Lazarowski et al., 1995; Pendergast et al., 2001; Yerxa et al., 2002) | |||
| Antagonist potencies | Suramin; PPADS insensitive (Charlton et al., 1996) | |||
| Radioligand assays | None | |||
| Radioligands | None | |||
| Transduction mechanism | Gq/G11, PLCβ, and possibly Gi/Go; PI hydrolysis (PLCβ activation) and elevated Ca2+ in expression systems; activation of IC1/Ca in Xenopus oocytes; transactivation of integrin and growth factor receptors (Soltoff, 1998; Erb et al., 2001; Seye et al., 2003; Liu et al., 2004) | |||
| Distribution | Quantitative RT-PCR: skeletal muscle, heart, and some brain regions; at more moderate levels spleen, lymphocytes, macrophages, bone marrow, and lung; lowest levels of mRNA in liver, stomach, and pancreas (Moore et al., 2001); vascular smooth muscle and endothelial cells (Ralevic and Burnstock, 1998) | |||
| Tissue function | Epithelial cell Cl— secretion (Clarke, 1992; Parr, 1994); pulmonary surfactant secretion (Rice, 1995); receptors on endothelial cells mediate NO release and subsequent vasodilatation (Ralevic and Burnstock, 1998); receptors on smooth muscle in some blood vessels mediate vasoconstriction (Ralevic and Burnstock, 1998); growth inhibition and apoptosis in human colorectal carcinoma cells (Burnstock and Knight, 2004); role in bone remodeling (Hoebertz et al., 2002); monocyte recruitment by vascular endothelium (Seye et al., 2003); proliferation of HeLa cells induced by c-Fos (Muscella, 2003); proliferation of lung cancer cells (Schafer, 2003); role in dry eye disease (Yerxa et al., 2002); regulation of proliferation in human keratinocyte (Burrel, 2003; Greig et al., 2003b); role in neutrophil degranulation (Meshki, 2004); growth of the arterial cell wall (Seye et al., 2002) | |||
| Phenotypes | Reduction of chloride secretion in airway epithelia P2Y2 knockout mice (Cressman et al., 1999) | |||
| Comments | The human P2Y2 receptor is activated by nucleotide triphosphates but not diphosphates (Nicholas et al., 1996) and is PPADS-insensitive (Charlton et al., 1996); P2Y2 receptor signaling is partially inhibited by PTX, indicating some involvement of Gi in receptor coupling (Parr et al., 1994)—in addition, native and recombinant forms of rat P2Y2 couple to PTX-sensitive Gi/o (Filippov et al., 1997; Mosbacher et al., 1998); Go activation by P2Y2 receptors requires integrin receptor transactivation (Erb et al., 2001); rabbit P2Y2 couples to Gi/Go isoforms (Murthy et al., 1998); *three transcript variants that encode the same protein have been identified for this gene (Parr et al., 1994); results of preclinical research suggest that P2Y2 receptor agonists inhibit Na absorption, restore C1 conductance, and rehydrate the cystic fibrosis airway surface (Kellermann, 2002); dCp4U (INS37217), a metabolically stable and potent P2Y2 agonist given for inhalation, has been evaluated in patients with cystic fibrosis lung disease (Kellerman et al., 2002); an RGD sequence in the P2Y2 receptor interacts with aVb3 integrins (Erb et al., 2001); Src homology 3 binding domains in the P2Y2 receptor activate Src and transactivate growth factor receptors (Erb et al., 2001; Seye et al., 2004); the C-terminal domain of the P2Y2 receptor mediates receptor desensitization and internalization (Garrad et al., 1998) | |||
aa, amino acids; AC, accession; chr., chromosome.