P2Y1 receptor (previously known as P2Y purinoceptor 1) 2.1:NUCT:1:P2Y1.
| TM | aa | AC | Chr. Map | References | |
|---|---|---|---|---|---|
| Human | 7 | 373 | NM_002563 | 3q25.2 | Ayyanathan et al. (1996); Léon et al. (1996) |
| Rat | 7 | 373 | NM_012800 | 2q31 | Tokuyama et al. (1995) |
| Mouse | 7 | 373 | NM_008772 | 3 | Tokuyama et al. (1995) |
| Functional assays | Measure of calcium fluxes in Jurkat T lymphocytes expressed the cloned P2Y1 receptor (Léon et al., 1997); human blood platelets; rat and rabbit mesenteric artery; turkey platelets | ||||
| Ligand | Action | Selectivity | Endogenous | References |
|---|---|---|---|---|
| 2-MeSADP | Agonist | No | No | Avyanathan et al. (1996); Palmer et al. (1998) |
| ADP | Agonist | No | Yes | Avyanathan et al. (1996); Palmer et al. (1998) |
| ATPγS | Agonist | No | No | Avyanathan et al. (1996); Palmer et al. (1998) |
| 2-MeSATP | Agonist | No | No | Avyanathan et al. (1996); Palmer et al. (1998) |
| ADPβS | Agonist | No | No | Avyanathan et al. (1996); Palmer et al. (1998) |
| ATP* | Partial agonist /antagonist | No | Yes | Avyanathan et al. (1996); Léon et al. (1997); Palmer et al. (1998) |
| ATP-α-B | Agonist | No | No | Nahum et al. (2002) |
| 2-MeSATP-α-B | Agonist | No | No | Nahum et al. (2002) |
| 2ClATP-α-B | Agonist | No | No | Nahum et al. (2002) |
| A3P5PS | Antagonist | No | No | Boyer et al. (1996a) |
| A3P5P | Antagonist | No | No | Hechler et al. (1998b) |
| A2P5P | Antagonist | No | No | Hechler et al. (1998b) |
| MRS2179 | Antagonist | Yes | No | Boyer et al. (1998); Camaioni et al. (1998); Baurand et al. (2001) |
| MRS2279 | Antagonist | Yes | No | Boyer et al. (1996a) |
| PPADS | Antagonist | No | No | Lambrecht et al. (2002) |
| Reactive blue 2 | Antagonist | No | No | Lambrecht et al. (2002) |
| Suramin | Antagonist | No | No | Lambrecht et al. (2002) |
| Agonist potencies | Ki values for P2Y1 receptor agonists for inhibition of [3H]MRS2279 binding to purified P2Y1 receptor: 2-MeSADP (Ki = 0.0099) > ADP (Ki = 0.92) > ATPγS (Ki = 1.33) > 2-MeSATP (Ki = 1.87) > ADPβS (Ki = 2.42) > ATP (Ki = 17.7) (Waldo and Harden, 2004) | |||
| Antagonist potencies | MRS2179 (pKB = 6.75 (Moro et al., 1998) (selective); MRS2279 (pKB = 8.10) (Boyer et al., 2002) (selective); reactive blue 2 (Lambrecht et al., 2002); PPADS (pKB = 5) (Guo et al., 2002); suramin (pKB = 5.5) (Ralevic and Burnstock, 1998); A3P5PS (pA2 = 6.5) (Boyer et al., 1996) | |||
| Radioligand assays | Equilibrium binding of [3H]MRS2279 to P2Y1 receptor expressed in membranes (Waldo et al., 2002; Waldo and Harden, 2004); binding studies with [33P]MRS2179 (Baurand et al., 2001) | |||
| Radioligands | [3H]MRS2279; [33P]MRS2179 | |||
| Transduction mechanism | Gq/G11; PI hydrolisis (PLC activation) and increasing of calcium in expression systems | |||
| Distribution | Brain, placenta, prostate, heart, skeletal muscle, platelets, neuronal tissue; P2Y1 mRNA could not be detected in cartilage and bone; it was expressed at barely detectable levels in liver, kidney, stomach, lymphocytes, and bone marrow (Moore et al., 2001) | |||
| Tissue function | Endothelium-dependent relaxation; smooth muscle relaxation (Ralevic and Burnstock, 1998); role in ADP-induced intracellular calcium mobilization, platelet shape change, aggregation, and TXA2 generation (Hechler et al., 1998a,1998b); mitogenic action in rat aorta smooth muscle (Ralevic and Burnstock, 1998); inhibition of N-type Ca2+ channels (Filippov et al., 2000); role of the receptor in nucleotide-mediated calcium signaling in astrocytes (Fumagalli et al., 2003); possible role in the modulation of neuro-neural signaling transmission (von Kügelgen and Wetter, 2000); role in osteoclastic bone resorption (Hoebertz et al., 2002) | |||
| Phenotypes | P2Y1-null mice* | |||
| Comments | In all species, the receptor is selective for adenine nucleotide;* these mice were viable with no apparent abnormalities that affected their development and survival; platelet count in these animals was identical to that of wild-type mice, but they were unable to aggregate in response to usual concentrations of ADP, whereas high concentrations of ADP induced platelet aggregation without shape change; P2Y1-null mice had no spontaneous bleeding tendency but were resistant to thromboembolism induced by intravenous injection of ADP (Fabre et al., 1999; Léon et al., 1999a); molecular modeling study of the human P2Y1 receptor supports the idea that ATP binding to at least two distinct domains of the P2Y1 receptor, both outside and within the TM core; the two disulfide bridges present in the human P2Y1 receptor play a major role in the structure and stability of the receptor, to constrain the loops within the receptor, specifically stretching the extracellular loop 2 over the opening of the TM cleft and thus defining the path of access to the binding site (Moro et al., 2002); MRS2179 is the first P2Y1 receptor antagonist with antithrombotic action (Baurand and Gachet, 2003) | |||
aa, amino acids; AC, accession; chr., chromosome; MRS2179, 2′-deoxy-N6-methyladenosine-3′,5′-bisphosphate; MRS2279, N6-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′ -bisphosphate; A3P5PS, adenosine-3′-phosphate-5′-phosphosulfate; A3P5P, adenosine 3′, 5′-diphosphate; A2P5P, adenosine 2′, 5′-diphosphate; ATP-α-B, 5′-O-(1-boranotriphosphate).