P2RX4: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m [Pu354]+: title, issue. Combined duplicate references. Formatted dashes.
Bcaruso54 (talk | contribs)
14 edits
I have reworked the structure of this page and have expanded the information to match the current research about P2rX4.
Line 3: Line 3:


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->

{{PBB_Summary
The product of this gene belongs to the family of [[Purinergic receptor|purinoceptors]] for [[Adenosine triphosphate|ATP]]. Multiple [[alternative splicing|alternatively spliced]] transcript variants have been identified for this gene although their full-length natures have not been determined.<ref name="entrez" />
| section_title =
| summary_text = The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with high calcium permeability. The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists [[suramin]] and PPADS. The product of this gene has the lowest sensitivity for these antagonists. Multiple alternatively spliced transcript variants have been identified for this gene although their full-length natures have not been determined.<ref name="entrez" />
}}
}}

The receptor is found in the central and peripheral nervous systems, in the epithelia of ducted glands and airways, in the smooth muscle of the [[bladder]], [[gastrointestinal tract]], [[uterus]], and [[Artery|arteries]], in uterine [[endometrium]], and in [[ adipocyte|fat cells]].<ref>{{cite pmid |12845522}}</ref> P2X<SUB>4</SUB> receptors have been implicated in the regulation of cardiac function, ATP-mediated [[apoptosis|cell death]], [[long-term potentiation|synaptic strengthening]], and activating of the [[inflammasome]] in response to injury.<ref>{{cite pmid | 22349510}}</ref><ref>{{cite pmid | 17264311}}</ref><ref>{{cite pmid | 16449800}}</ref><ref>{{cite pmid | 21749490}}</ref><ref>{{cite pmid | 22378878}}</ref>

==Receptor Structure and Kinetics==
The P2X<SUB>4</SUB> subunits can form [[homomeric]] or [[heteromeric]] receptors.<ref>{{cite pmid | 22547202}}</ref> The P2X<SUB>4</SUB> receptor has a typical [[P2X purinoreceptor|P2X receptor]] structure. Interestingly, the P2X receptor structure was discovered through the use of [[X-ray crystallography]] to resolve the three-dimensional structure of the [[zebrafish]] P2X<SUB>4</SUB> receptor.<ref>{{cite pmid | 19641588}}</ref>
The P2X<SUB>4</SUB> receptor is a [[ligand-gated ion channel|ligand-gated cation channel]] that opens in response to ATP binding.<ref>{{cite pmid | 12270951}}</ref> The P2X<SUB>4</SUB> receptor has high [[calcium]] permeability, leading to the [[depolarization]] of the cell membrane and the activation of various Ca<sup>2+</sup>-sensitive intracellular processes.<ref>{{cite pmid| 12270951}}</ref><ref>{{cite pmid |15044552}}</ref><ref>{{cite pmid |11040040}}</ref> Continued binding leads to increased permeability to N-methyl-D-glucamine (NMDG<sup>+</sup>) in about 50% of the cells expressing the P2X<SUB>4</SUB> receptor.<ref>{{cite pmid | 12270951}}</ref> The [[Desensitization (medicine)|desensitization]] of P2X<SUB>4</SUB> receptors is intermediate when compared to [[P2RX1|P2X1]] and [[P2RX2P2X2]] receptors.<ref>{{cite pmid|12270951}}</ref>

==Pharmacology==
===Agonists===
P2X<SUB>4</SUB> receptors respond to ATP, but not αβmeATP. These receptors are also potentiated by [[ivermectin]], cibacron blue, and [[zinc]].<ref>{{cite pmid | 12270951}}</ref>

===Antagonists===
The main pharmacological distinction between the members of the [[Purinergic receptor|purinoceptor]] family is the relative sensitivity to the antagonists [[suramin]] and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid ([[PPADS]]). The product of this gene has the lowest sensitivity for these antagonists<ref>{{cite pmid| 12270951}}</ref>

==Receptor Trafficking==
P2X<SUB>4</SUB> receptors are stored in [[lysosome]]s and brought to the cell surface in response to extracellular signals.<ref>{{cite pmid | 17940064}}</ref> These signals include [[Interferon-gamma|IFN-γ]], [[CCL21]], [[CCL2]]. <ref>{{cite pmid | 19380717}}</ref><ref>{{cite pmid | 21441897}}</ref><ref>{{cite pmid | 22222817}}</ref> [[Fibronectin]] is also involved in upregulation of P2X<SUB>4</SUB> receptors through interactions with [[integrin]]s that lead to the activation of [[src gene|SRC-family kinase]] member, [[Lyn src family kinase|Lyn]].<ref>{{cite pmid | 17918263}}</ref> Lyn then activates [[PI3K/AKT/mTOR|PI3K-AKT]] and [[ MAPK/ERK|MEK-ERK]] signaling pathways to stimulate receptor trafficking.<ref>{{cite pmid | 19298529}}</ref> Internalization of P2X<SUB>4</SUB> receptors is [[clathrin]]- and [[dynamin]]-dependent [[endocytosis]].<ref>{{cite pmid | 12105201}}</ref>

==Neuropathic Pain==
The P2X<SUB>4</SUB> receptor has been linked to [[neuropathic pain]] mediated by [[microglia]] ''[[in vitro]]'' and ''[[in vivo]]''.<ref>{{cite pmid | 20562826}}</ref><ref>{{cite pmid | 19515262}}</ref> P2X<SUB>4</SUB> receptors are upregulated following injury.<ref>{{cite pmid | 18971468}}</ref> This upregulation allows for increased activation of [[p38 mitogen-activated protein kinases]], thereby increasing the release of brain-derived neurotrophic factor ([[Brain-derived neurotrophic factor|BDNF]]) from microglia.<ref>{{cite pmid | 19295157}}</ref> BDNF released from microglia induces neuronal hyperexcitability through interaction with the [[TrkB receptor]].<ref>{{cite pmid | 16355225}}</ref> More importantly, recent work shows that P2X<SUB>4</SUB> receptor activation is not only necessary for neuropathic pain, but it is also sufficient to cause neuropathic pain.<ref>{{cite pmid | 12917686}}</ref>


==See also==
==See also==

Revision as of 22:29, 29 April 2013

Template:PBB P2X purinoceptor 4 is a protein that in humans is encoded by the P2RX4 gene.[1][2]


The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced transcript variants have been identified for this gene although their full-length natures have not been determined.[2] }}

The receptor is found in the central and peripheral nervous systems, in the epithelia of ducted glands and airways, in the smooth muscle of the bladder, gastrointestinal tract, uterus, and arteries, in uterine endometrium, and in fat cells.[3] P2X4 receptors have been implicated in the regulation of cardiac function, ATP-mediated cell death, synaptic strengthening, and activating of the inflammasome in response to injury.[4][5][6][7][8]

Receptor Structure and Kinetics

The P2X4 subunits can form homomeric or heteromeric receptors.[9] The P2X4 receptor has a typical P2X receptor structure. Interestingly, the P2X receptor structure was discovered through the use of X-ray crystallography to resolve the three-dimensional structure of the zebrafish P2X4 receptor.[10] The P2X4 receptor is a ligand-gated cation channel that opens in response to ATP binding.[11] The P2X4 receptor has high calcium permeability, leading to the depolarization of the cell membrane and the activation of various Ca2+-sensitive intracellular processes.[12][13][14] Continued binding leads to increased permeability to N-methyl-D-glucamine (NMDG+) in about 50% of the cells expressing the P2X4 receptor.[15] The desensitization of P2X4 receptors is intermediate when compared to P2X1 and P2RX2P2X2 receptors.[16]

Pharmacology

Agonists

P2X4 receptors respond to ATP, but not αβmeATP. These receptors are also potentiated by ivermectin, cibacron blue, and zinc.[17]

Antagonists

The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). The product of this gene has the lowest sensitivity for these antagonists[18]

Receptor Trafficking

P2X4 receptors are stored in lysosomes and brought to the cell surface in response to extracellular signals.[19] These signals include IFN-γ, CCL21, CCL2. [20][21][22] Fibronectin is also involved in upregulation of P2X4 receptors through interactions with integrins that lead to the activation of SRC-family kinase member, Lyn.[23] Lyn then activates PI3K-AKT and MEK-ERK signaling pathways to stimulate receptor trafficking.[24] Internalization of P2X4 receptors is clathrin- and dynamin-dependent endocytosis.[25]

Neuropathic Pain

The P2X4 receptor has been linked to neuropathic pain mediated by microglia in vitro and in vivo.[26][27] P2X4 receptors are upregulated following injury.[28] This upregulation allows for increased activation of p38 mitogen-activated protein kinases, thereby increasing the release of brain-derived neurotrophic factor (BDNF) from microglia.[29] BDNF released from microglia induces neuronal hyperexcitability through interaction with the TrkB receptor.[30] More importantly, recent work shows that P2X4 receptor activation is not only necessary for neuropathic pain, but it is also sufficient to cause neuropathic pain.[31]

See also

References

  1. ^ Garcia-Guzman M, Soto F, Gomez-Hernandez JM, Lund PE, Stuhmer W (1997). "Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue". Mol Pharmacol. 51 (1): 109–18. PMID 9016352. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ a b "Entrez Gene: P2RX4 purinergic receptor P2X, ligand-gated ion channel, 4".
  3. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12845522, please use {{cite journal}} with |pmid=12845522 instead.
  4. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22349510, please use {{cite journal}} with |pmid= 22349510 instead.
  5. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17264311, please use {{cite journal}} with |pmid= 17264311 instead.
  6. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16449800, please use {{cite journal}} with |pmid= 16449800 instead.
  7. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21749490, please use {{cite journal}} with |pmid= 21749490 instead.
  8. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22378878, please use {{cite journal}} with |pmid= 22378878 instead.
  9. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22547202, please use {{cite journal}} with |pmid= 22547202 instead.
  10. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19641588, please use {{cite journal}} with |pmid= 19641588 instead.
  11. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid= 12270951 instead.
  12. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid= 12270951 instead.
  13. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15044552, please use {{cite journal}} with |pmid=15044552 instead.
  14. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11040040, please use {{cite journal}} with |pmid=11040040 instead.
  15. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid= 12270951 instead.
  16. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid=12270951 instead.
  17. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid= 12270951 instead.
  18. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12270951, please use {{cite journal}} with |pmid= 12270951 instead.
  19. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17940064, please use {{cite journal}} with |pmid= 17940064 instead.
  20. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19380717, please use {{cite journal}} with |pmid= 19380717 instead.
  21. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21441897, please use {{cite journal}} with |pmid= 21441897 instead.
  22. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22222817, please use {{cite journal}} with |pmid= 22222817 instead.
  23. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17918263, please use {{cite journal}} with |pmid= 17918263 instead.
  24. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19298529, please use {{cite journal}} with |pmid= 19298529 instead.
  25. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12105201, please use {{cite journal}} with |pmid= 12105201 instead.
  26. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20562826, please use {{cite journal}} with |pmid= 20562826 instead.
  27. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19515262, please use {{cite journal}} with |pmid= 19515262 instead.
  28. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18971468, please use {{cite journal}} with |pmid= 18971468 instead.
  29. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19295157, please use {{cite journal}} with |pmid= 19295157 instead.
  30. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16355225, please use {{cite journal}} with |pmid= 16355225 instead.
  31. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12917686, please use {{cite journal}} with |pmid= 12917686 instead.

Further reading

Template:PBB Further reading

External links

Stub icon

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Template:PBB Controls

Retrieved from "https://en.wikipedia.org/w/index.php?title=P2RX4&oldid=552798019"