Table 1.
Key facts and the useful pharmacopeia for exploring P2X receptors.
| P2X1 | P2X2 | P2X3 | P2X4 | P2X5 | P2X6 | P2X7 | |
|---|---|---|---|---|---|---|---|
| Gene name | P2RX1 | P2RX2 | P2RX3 | P2RX4 | P2RX5 | P2RX6 | P2RX7 |
| Desensitization (complete in) | Fast (<1s) | Slow (>20s) | Fast (<1s) | Slow (>20s) | Slow (>20s) | _ | Slow (>20s) |
| Pore “dilation” | No | Yes | No | Yes | _ | _ | Yes |
| PCa/PNa | 4.8 | 2.8 | 1.2 | 4.2 | 1.5 | _ | _ |
| Fractional Ca2+ current (%) | 12.4 | 5.7 | 2.7 | 11 | 4.5 | _ | 4.6 |
| KO made | Yes | Yes | Yes | Yes | _ | _ | Yes |
| Agonist EC50 values (µM) | |||||||
| ATP | 0.07 | 1.2 | 0.5 | 10 | 10 | 12 | 100 |
| 2MeSATP | 0.07 | 1.2 | 0.3 | 10 | 10 | 9 | 100 |
| αβmeATP | 0.3 | > 300 | 0.8 | > 300 | > 300 | > 100 | > 300 |
| BzATP | 0.003 | 0.75 | 0.08 | 7 | > 500 | - | 20 |
| Antagonist IC50 values (µM) | |||||||
| Suramin | 1 | 10 | 3 | >500 | 4 | >100 | 500 |
| PPADS | 1 | 1 | 1 | >500 | 3 | >100 | 50 |
| TNP-ATP | 0.006 | 1 | 0.001 | 15 | - | - | > 30 |
| IP5I | 0.003 | > 300 | 2.8 | Potentiation | - | - | |
| A-317491 | > 10 | > 100 | 0.10 | > 100 | - | > 100 | > 100 |
| RO-3 | > 100 | > 100 | 0.10 | > 100 | > 100 | > 100 | |
| A-740003 | > 100 | > 100 | > 100 | > 100 | - | > 100 | 0.05 |
| AF-353 | > 10 | > 10 | 0.01 | > 10 | > 10 | > 10 | |
| A-438079 | > 100 | > 100 | > 100 | > 100 | - | > 100 | 0.06 |
| A-804598 | > 100 | > 100 | > 100 | > 100 | - | > 100 | 0.01 |
| MRS2179 | 80 | > 100 | > 100 | - | - | > 100 | |
| NF279 | 9 | 30 | 50 | > 100 | - | - | 20 |
| NF449 | 0.7 | > 100 | >100 | > 100 | - | - | > 100 |
| Modulator EC50 values (µM) | |||||||
| Ivermectin | - | > 30 | > 30 | 0.25 | - | - | > 30 |
| Zn2+ | - | Increase EC50 = 7µM | - | Increase 2µM | - | - | - |
| H+ | Decrease pKa 6.3 | Increase pKa 7.3 | Decrease pKa 6.0 | Decrease pKa 6.8 | - | - | Decrease pKa 6.1 |
Notes for table 1: -Indicates that this information is not yet available. The Pf(%) values are for the rat subunits, but the pCa2+/pNa+ values are also shown for human and rat isoforms as appropriate for the available data. In the case of suramin and PPADS IC50 values the data for P2X4 are highly species-dependent.
Abbreviations used in the table: ATP: adenosine 5’-triphosphate, 2meSATP: 2-methythioadenosine 5’-triphosphate, α,βmeATP: alpha beta methylene adenosine 5’-triphosphate, BzATP: 2,3-O-(4-benzoylbenzoyl)-ATP, PPADS: pyridoxal-5’-phosphate-6-azophenyl-2’,4’-disulphonic acid, TNP-ATP: 2’,3’-O-(2,4,6-Trinitrophenyl) adenosine 5’-triphosphate, IP5I: Diinosine pentaphosphate, A-317491: 5-({(3-phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino}carbonyl)-1,2,4-benzenetricarboxylic acid RO-3: 5-(2-isopropyl-4,5-dimethoxybenzyl)pyrimidine-2,4-diamine, A-740003: N-[1-(N"-cyano-N'-quinolin-5-ylcarbamimidamido)-2,2-dimethylpropyl]-2-(3,4-dimethoxyphenyl)acetamide, AF-353: 5-(5-iodo-2-isopropyl-4-methoxyphenoxy)-pyrimidine-2,4-diamine, A-438079: 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine, A-804598: 2-Cyano- 1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine, MRS2179: 2’-deoxy-N6-methyl adenosine 3’,5’diphosphate, NF279: 8,8’-(carbonylbis(imino-4-1-phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis(naphthalene)-1,3,5-trisulfonic acid, NF449: 4-[({3-[({3,5-bis[(2,4-disulfophenyl)carbamoyl]phenyl}carbamoyl)amino]-5-[(2,4-disulfophenyl)carbamoyl]phenyl}carbonyl)amino]benzene-1,3-disulfonic acid.