P2X Receptor
From Wikipedia, the free encyclopedia
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P2X2 receptor (Homo sapiens)
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| Identifiers | |
| Symbol(s) | P2RX2 P2X2R |
| Entrez | 22953 |
| OMIM | 600844 |
| RefSeq | [1] |
| UniProt | Q9UBL9 |
| Other data | |
| Locus | Chr. 12 q24.33 |
P2X receptors are a family of cation-permeable ligand gated ion channels that open in response to extracellular adenosine 5'-triphosphate (ATP). They belong to a larger family of receptors known as the purinergic receptors; so called because they are activated by purine-containing compounds such as adenosine and the nucleotides ATP and UTP. The other members of the purine receptor group are the nucleotide-activated P2Y receptors and the adenosine-activated P1 receptors, although these are G protein-coupled receptors rather than ligand-gated ion channels.
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[edit] Basic Structure and Nomenclature
Each functional P2X receptor is made up of three protein subunits. To date, seven separate genes coding for P2X subunits have been identified, and referred to as P2X1 through P2X7. The three subunits making up the assembled P2X receptor channel are arranged to form a gated, ion-permeable pore. The subunits all share a common topology, possessing two plasma membrane spanning domains, a large extracellular loop and intracellular carboxyl and amino termini. With the exception of P2X6, each subunit can readily form a functional homomeric receptor. A P2X receptor made up of only P2X1 subunits is simply termed a P2X1 receptor. The general consensus is that P2X6 cannot form a functional homomeric receptor when expressed alone, but nevertheless can co-assemble with other subunits to form functional heteromeric receptors. With the exception of P2X7, all of the P2X subunits are capable of forming heteromeric P2X receptors with at least one other subunit type. A P2X receptor made up of P2X2 and P2X3 subunits is known as the P2X2/3 receptor.
[edit] Activation and Channel Opening
ATP binds to the extracellular loop of the P2X receptor, whereupon it evokes a conformational change in the structure of the ion channel that results in the opening of the ion-permeable pore. This allows cations such as Na+ and Ca2+ to enter the cell, leading to depolarization of the cell membrane and the activation of various Ca2+-sensitive intracellular processes. At least three ATP molecules are required to activate a P2X receptor, suggesting that ATP needs to bind to each of the three subunits in order to open the channel pore. The precise mechanism by which the binding of ATP leads to the opening of the P2X receptor channel pore is not well understood, but is currently under investigation.
[edit] Pharmacology
The pharmacology of a given P2X receptor is largely determined by its subunit makeup. For example, P2X1 and P2X3 receptors desensitize rapidly in the continued presence of ATP, whereas the P2X7 receptor channel mostly remains open for as long as ATP is bound to it. The different subunits also exhibit different sensitivities to purinergic agonists such as ATP, α,β-MeATP and BzATP; and antagonists such as pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and suramin (North, 2002). Of continuing interest is the fact that some P2X subunits confer the ability for the P2X receptor channel to dilate during prolonged exposure to ATP, thus forming a pore permeable to relatively large molecules such as N-methyl-D-glucamine and propidium iodide analogs (Khakh et al., 1999).
[edit] Tissue Distribution
P2X receptors are expressed in cells from a wide variety of animal tissues. On presynaptic and postsynaptic nerve terminals throughout the central, peripheral and autonomic nervous systems, P2X receptors have been shown to modulate synaptic transmission. Furthermore, P2X receptors are able to initiate contraction in cells of the heart muscle, skeletal muscle, and various smooth muscle tissues, including that of the vasculature, vas deferens and urinary bladder. P2X receptors are also expressed on leukocytes, including lymphocytes and macrophages, and are present on blood platelets. There is some degree of subtype specificity as to which P2X receptor subtypes are expressed on specific cell types, with P2X1 receptors being particularly prominent in smooth muscle cells, and P2X2 being widespread throughout the autonomic nervous system. However, such trends are very general and there is considerable overlap in subunit distribution, with most cell types expressing more than one subunits. For example, P2X2 and P2X3 subunits are commonly found co-expressed in sensory neurons, where they often co-assemble into functional P2X2/3 receptors.
[edit] Physiological Roles
In keeping with their wide distribution throughout the body, P2X receptors are involved in a variety of phsyiological processes, including:
- Modulation of cardiac rhythm and contractility
- Modulation of vascular tone
- Mediation of nociception
- Contraction of the vas deferens during ejaculation
[edit] See also
[edit] External links
[edit] References
1. Burnstock, G. (2000). P2X receptors in sensory neurones. British Journal of Anaesthesia. 84: 476-88. Free article (.pdf) available here.
2. Chizh, B.A. & Illes, P. (2001). P2X receptors and nociception. Pharmacological Reviews. 53:553-68. Free article available online.
3. North, R.A. (2002) Molecular Physiology of P2X receptors. Physiological Reviews. 83:1013-67. Free article available online..
4. Khakh, B.S., Bao, X.R., Labarca C. & Lester, H.A. (1999).Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nature Neuroscience. 2:322-30. Available online, but subscription required.
5. Samways, D.S., Li, Z., & Egan, T.M. (2006). Binding, gating and conduction of ATP-gated P2X receptor channels. Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies. Chapter 16:419-443.
6. Vassort, G. (2001). Adenosine 5'-triphosphate: a P2-purinergic agonist of the myocardium. Physiological Reviews. 81:767-806. Free article available online.
7. Vial, C., Roberts, J.A., & Evans, R.J. (2004). Molecular properties of ATP-gated P2X receptor ion channels. Trends in Pharmacological Sciences. 25:487-93. Available online, but subscription required.
