P2Y4 receptor (previously known as P2Y purinoceptor 4 and uridine nucleotide receptor) 2.1:NUCT:3:P2Y4
| TM | aa | AC | Chr. Map | References | |
|---|---|---|---|---|---|
| Human | 7 | 365 | NM_002565 | Xq13 | Nguyen et al. (1995) |
| Rat | 7 | 361 | NM_031680 | Xq31 | Bogdanov et al. (1998b) |
| Mouse | 7 | 361 | NM_020621 | X | Lazarowski et al. (2001) |
| Functional assays | Calcium mobilization in 1321N1 astrocytoma cells that express recombinant receptor (Communi et al., 1995); Nguyen et al., 1995) | ||||
| Ligand | Action | Selectivity | Endogenous | References |
|---|---|---|---|---|
| UTP | Agonist | No | Yes | Communi et al. (1995) |
| UTPγS | Agonist | No | No | Jacobson et al. (2002) |
| 5BrUTP | Agonist | No | No | Nguyen et al. (1995) |
| UDP | Partial agonist | No | Yes | Nguyen et al. (1995) |
| ITP | Partial agonist | No | No | Communi et al. (1995) |
| ATP* | Agonist/antagonist | No | Yes | Herold et al. (2004) |
| PPADS | Antagonist | No | No | Charlton et al. (1996) |
| Reactive blue 2 | Antagonist | No | No | Brown et al. (2002) |
| Agonist potencies | Human: UTP (EC50 = 2.5 μM) > ITP (33 μM) (Communi et al., 1996a); rat: ITP (EC50 = 1.4 μM) = ATP (1.8 μM) = UTP (2.6 μM) (Bogdanov et al., 1998b) | |||
| Antagonist potencies | Human: PPADS (25% reduction at 100 μM) (Charlton et al., 1996); ATP is a competitive antagonist (Kennedy et al., 2000); rat: reactive blue 2 (IC50 = 21 μM) (Bogdanov et al., 1998b) | |||
| Radioligand assays | None | |||
| Radioligands | None | |||
| Transduction mechanism | Gq/G11 and possibly GI; PI hydrolysis (PLCβ activation) and elevated [Ca2+]i in expression systems; activation of ICl/Ca in Xenopus oocytes (by increased [Ca2+]i); inhibition of N-type Ca2+ and M-type K+ channels (Filippov et al., 2003) | |||
| Distribution | Quantitative RT-PCR: high levels of mRNA in intestine, pituitary, and brain; low levels in liver and bone marrow (Moore et al., 2001); monocyte and lymphocytes (Jin et al., 1998b) | |||
| Tissue Function | Endothelial cell receptors mediate NO release and subsequent vasodilatation (Burnstock et al., 2002); mitogenic actions on vascular smooth muscle cells (Burnstock et al., 2002); regulation of epithelial chloride transport in jejunum (Robaye, 2003) | |||
| Phenotypes | Loss of nucleotide regulation of epithelial Cl— transport in the jejunum of null mice (Robaye et al., 2003) | |||
| Comments | When expressed in a mammalian cell line, this receptor was activated specifically by UTP > UDP but not by ATP and ADP (Communi et al., 1995; Nguyen et al., 1995); competitive; a recent study shows that ATP is a potent antagonist at the hP2Y4, whereas it is a full agonist at the rat P2Y4 (Herold et al 2004)*; rat P2Y4 is not selective for uridine nucleotides and instead shows an agonist potency order of ATP = UTP; ADP, ATPγS, 2-MeSATP, and UDP are partial agonists (Bogdanov et al., 1998b; Webb et al., 1998); both human and rat P2Y4 are suramin-insensitive (Charlton et al., 1996); UTP regulates ion transport in jejunum (Cressman et al., 1999)—the disappearance of the jejunal Cl— secretory response to UTP and ATP in P2Y4-null mice demonstrates the involvement of the P2Y4 receptor; P2Y4 receptors might be considered a potential pharmacotherapeutic target for cystic fibrosis (Robaye et al., 2003) | |||
aa, amino acids; AC, accession; chr., chromosome.