Purinergic (P2X) Receptors

P2X purinergic receptors are ATP-gated ion channels composed of three subunits, which confer specific receptor subtype pharmacology, and are permeable to cations. Binding of ATP results in channel opening, cation influx and membrane depolarization. These receptors are widely distributed throughout the body, and most cell types express more than one P2X receptor subtype. P2X receptors play physiological roles in a wide range of processes such as modulation of synaptic transmission, vascular tone, cardiac rhythm and contractility, immune response.

Products
Background
Literature (5)
Gene Data

Purinergic (P2X) Receptor Agonists

Cat. No. Product Name / Activity
3245 ATP disodium salt
Endogenous P2 purinergic agonist
4080 ATPγS tetralithium salt
Non-selective P2 agonist; analog of ATP (Cat. No. 3245)
3312 BzATP triethylammonium salt
P2X7 agonist; also P2X1 and P2Y1 partial agonist
3209 α,β-Methyleneadenosine 5'-triphosphate trisodium salt
Non-selective P2 agonist
1062 2-Methylthioadenosine triphosphate tetrasodium salt
Non-selective P2 agonist

Purinergic (P2X) Receptor Antagonists

Cat. No. Product Name / Activity
6493 A 317491 sodium salt
Selective, high affinity P2X3 and P2X2/3 antagonist; antinociceptive
2972 A 438079 hydrochloride
Competitive P2X7 antagonist
3701 A 740003
Potent and selective P2X7 antagonist
4473 A 804598
Potent and selective P2X7 antagonist
4232 A 839977
Potent P2X7 antagonist
3323 AZ 10606120 dihydrochloride
Potent P2X7 antagonist
3317 AZ 11645373
Potent and selective human P2X7 antagonist
3579 5-BDBD
Potent and selective P2X4 antagonist
5545 BX 430
Selective P2X4 allosteric antagonist
0845 Evans Blue tetrasodium salt
P2X antagonist; also non-NMDA iGluR antagonist; inhibits L-glutamate uptake into synaptic vesicles
2611 IMD 0354
P2X1, P2X4 and P2X7 antagonist; also inhibitor of IKKβ
5299 JNJ 47965567
Potent and selective P2X7 antagonist; brain penetrant
1277 KN-62
Non-competitive P2X7 antagonist
1240 NF 023
Selective and competitive P2X1 antagonist
2548 NF 110
Potent P2X3 antagonist
2450 NF 157
Selective P2Y11 and P2X1 antagonist
1199 NF 279
Potent and selective P2X1 antagonist
1391 NF 449
Highly selective P2X1 antagonist
0625 PPADS tetrasodium salt
Non-selective P2 antagonist
0683 iso-PPADS tetrasodium salt
Non-selective P2X antagonist
1309 PPNDS
Potent and selective P2X1 antagonist
2188 Ro 0437626
Selective P2X1 antagonist
4391 Ro 51
Potent P2X3 and P2X2/3 antagonist
3052 RO-3
Selective P2X3 and P2X2/3 antagonist
4386 TC-P 262
Selective P2X3 and P2X2/3 antagonist
2464 TNP-ATP triethylammonium salt
Potent and selective P2X antagonist

Purinergic (P2X) Receptor Modulators

Cat. No. Product Name / Activity
3385 GW 791343 hydrochloride
Allosteric modulator of P2X7 receptors
1260 Ivermectin
Positive allosteric modulator of P2X4 receptors

Other

Cat. No. Product Name / Activity
5157 DMNPE-caged ATP diammonium salt
Caged ATP

P2X Purinergic Receptor Subunits

Each functional P2X receptor is formed from either three identical subunits (homomeric) or a combination of two or three different subunits (heteromeric). Except for P2X6, all subunits can form homomeric receptors, however, P2X7 subunits only form homomeric receptors. Functional receptors are named for their constituent subunits, for example a homomeric receptor composed of P2X7 subunits is called a P2X7 receptor, while a heteromeric receptor composed of P2X2 and P2X3 subunits is called a P2X2/3 receptor.

Human homomeric P2X<sub>3</sub> receptor  protein structure

Figure 1: Structure of human homomeric P2X3 receptor. Structure taken from PDB. PDBID: 5SVQ. Mansoor et al (2016) X-ray structures define human P2X3 receptor gating cycle and antagonist action. Nature 538: 66-71

Three molecules of ATP are required for channel opening, with one binding to each subunit. P2X receptors are highly selective for ATP over other purines and pyrimidines such as ADP and UTP, which activate P2Y receptors. ATP binding causes a conformational change in the ion channel structure that opens the pore and allows cations to pass through the cell membrane. The specific subunit confirmation of a receptor determines channel opening time; for example P2X1 and P2X3 receptors desensitize within a few 100 ms but for P2X7 receptors there is little decrease in ionic current flow even over several minutes.

The subunit conformation of a receptor also determines its pharmacology; different subunits have different sensitivities to P2X agonists, such as ATP (Cat. No. 3245) and α,β-meATP (Cat. No. 3209) and P2X antagonists, such as PPADS (Cat. No 0625) and TNP-ATP (Cat. No. 2464). The sensitivity of a P2X receptor to ATP is heavily affected by changes in extracellular pH and by heavy metals, due to the presence of histidine side chains in the receptor's extracellular domains. An extracellular pH <7 attenuates ATP sensitivity at P2X1, P2X3 and P2X4 receptors but increases P2X2 receptor ATP sensitivity. In contrast, zinc potentiates ATP-gated currents through P2X2, P2X3 and P2X4, and inhibits currents through P2X1 receptors.

P2X Purinergic Receptor Distribution

P2X receptors have a wide distribution throughout the body and are found at neuromuscular junctions in the central and peripheral nervous system including the spinal cord, in smooth muscle, in the heart, and on leukocytes. In the brain, P2X receptors are found at pre- and post-synaptic membranes where they modulate neurotransmitter release. In general, different P2X receptor subtypes don't display tissue specificity and there is a large overlap in subunit distribution, with most cells expressing more than one receptor subtype.

Their extensive distribution means P2X receptors are involved in a diverse range of physiological processes, including modulation of synaptic transmission, modulation of vascular tone, cardiac rhythm and contractility, nociception and chronic pain, contraction of the bladder, and immune response.

P2X7 receptors are of interest in cancer immunology as they are overexpressed in tumors. Elevated intratumoral ATP levels acting via P2X7 receptors on myeloid-derived suppressor cells (MDSCs), result in immunosuppression.

P2X Purinergic Receptors & Nociception

P2X3 and P2X2/3 receptors have been well studied for their role in nociception. They are highly expressed on sensory neurons in dorsal root ganglia in the spinal cord, and are also found at nociceptive nerve terminal in the periphery where they respond to increased extracellular ATP from various sources including tumors and the vascular endothelium. Similarly, activation of P2X and P2Y receptors on glial cells (astrocytes and microglial) are thought to indirectly modulate nociception. Research has suggested that the expression of these receptors on nociceptive nerve terminals and glial cells contributes to the development and maintenance of various forms of neuropathic and inflammatory pain. The selective P2X2 and P2X2/3 receptor antagonist A 317491 (Cat. No. 6493) displays antinociceptive activity in multiple different pain paradigms including neuropathic, inflammatory and chronic pain states, in animal models.

External sources of pharmacological information for Purinergic (P2X) Receptors :

Literature for Purinergic (P2X) Receptors

Tocris offers the following scientific literature for Purinergic (P2X) Receptors to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


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P2X Receptor Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
P2X1 Human P2RX1 NM_002558 P51575
Mouse P2rx1 NM_008771 P51576
Rat P2rx1 NM_012997 P47824
P2X2 Human P2RX2 NM_174873 Q9NR38
Mouse P2rx2 NM_153400 NP_700449
Rat P2rx2 NM_053656 P49653
P2X3 Human P2RX3 NM_002559 P56373
Mouse P2rx3 NM_145526 Q3UR32
Rat P2rx3 NM_031075 P49654
P2X4 Human P2RX4 NM_175567 Q99571
Mouse P2rx4 NM_011026 Q9JJX6
Rat P2rx4 NM_031594 P51577
P2X5 Human P2RX5 NM_002561 Q93086
Mouse P2rx5 NM_033321 NP_201578
Rat P2rx5 NM_080780 P51578
P2X6 Human P2RX6 NM_005446 O15547
Mouse P2rx6 NM_011028 O54803
Rat P2rx6 NM_012721 P51579
P2X7 Human P2RX7 NM_002562 Q99572
Mouse P2rx7 NM_011027 Q9Z1M0
Rat P2rx7 NM_019256 Q64663