Disease relevance of P2rx2

• These data indicate that modulation of P2X2 receptor function, such as that evoked by acidification of the extracellular environment during hypercapnia, may contribute to the changes in activity of the VLM respiratory neurones that express these receptors [1].
• Approximately 60%, 70% and 50% of the ganglion cells in the myenteric plexus of the gastric corpus, ileum and distal colon, and 56% and 45% in the submucosal plexus of the ileum and distal colon, respectively, showed positive immunoreactivity to the P2X2 receptor [2].
• A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in rats [3].
• Hence, alpha,beta-meATP-sensitive P2X3 and/or P2X2/3 receptors of L6/S1 dorsal root ganglion neurons were functionally downregulated during subacute pain caused by experimental cystitis [4].
• This condition might also occur on P2X2 receptors of central neurons exposed to low pH during ischemia [5].

High impact information on P2rx2

• Sensitivity to two of these antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and pyridoxal 5-phosphate) is restored by replacement of Glu249 by lysine, which occurs at the equivalent position in P2X1 and P2X2 receptors [6].
• Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons [7].
• Our results demonstrate for the first time the presence of functional ionotropic P2X purinoceptors in the cerebellar Purkinje cells and indicate that their pharmacology is similar to receptors formed by P2X2 subunit oligomers [8].
• To probe the location of this zinc binding site, P2X2 receptors bearing mutations of the histidines at positions 120 and 213 were expressed in Xenopus oocytes [9].
• Taken together, these data indicate that His120 and His213 sit close to each other across the interface between subunits and are likely to be key components of the zinc binding site in P2X2 receptors [9].

Biological context of P2rx2

• In the excretory ducts of the testis (ductus epididymidis, vas deferens and its associated seminal vesicles), the major signals were seen with antibodies to P2X1 and P2X2 in the membranes of the smooth muscle layer, suggesting that these receptors are involved in the process of sperm transport and ejaculation [10].
• These results suggested that P2 receptors, especially the P2X2 receptors, may play important roles in the signal transduction involved in the perception of sound and balance [11].
• Furthermore, we identified by mutagenesis study that Ile328 located at the outer mouth of the pore is critical for the density-dependent changes of P2X2 [12].
• Noise induces up-regulation of P2X2 receptor subunit of ATP-gated ion channels in the rat cochlea [13].
• The P2X2 purinergic receptor permeates cationic ions in response to stimulation by ATP and mediates fast synaptic transmission [14].

Anatomical context of P2rx2

• The smooth muscle of some capsular and subcapsular blood vessels showed P2X2 immunoreactivity [15].
• The present study revealed the presence of P2X2, P2X3, P2X4 and P2X7-mRNA in rat organ of Corti, vestibular organ and spiral ganglion at different postnatal developmental stages (PD1-PD16), with slight differences in the onset of expression [16].
• In the penis body, strong P2X1 and weaker P2X2 immunoreactivity was seen in the smooth muscle of blood vessels and the corpus cavernosum, suggesting a participation in the detumescence process [10].
• P2X2 receptors were found on subcapsular and perivascular epithelial cells [17].
• In nodose ganglion, both P2X2 and P2X3 antibodies labelled the neurones intensely [18].

Associations of P2rx2 with chemical compounds

• We investigated the effect of 100 microM ATP and alpha,beta-methylene ATP (alpha,beta-meATP; selective agonist for P2X1, P2X2/3 and P2X3 receptors) on motor axon outgrowth in collagen-embedded neural tube explant cultures [19].
• Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels [20].
• Non-additive responses observed between cation-selective GABAA and P2X2 receptors further indicate the chloride independence of this process [20].
• DHEA also potentiated putative homomeric P2X2 receptor responses recorded in the continuous presence of 1 microM 2'-(or 3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP) [21].
• Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones [21].

Regulatory relationships of P2rx2

• 4. In situ hybridization revealed that small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed mRNAs of P2X2 and P2X3 [22].
• Double-labelling studies showed that about 10-25% of the neurons with P2X2 immunoreactivity in myenteric plexus and 30-50% in the submucosal plexus were found to express calbindin or calretinin [2].

Other interactions of P2rx2

• ATP elicits inward currents in isolated vasopressinergic neurohypophysial terminals via P2X2 and P2X3 receptors [23].
• Antibodies against P2X2 and P2X4 labeled both astroglial cell bodies and processes [24].
• We further examined the coexpression of all pairs of P2X2-P2X6 mRNAs in DRG neurons and found that: 1) P2X4 was always present in combination with the other subunits [25].
• During development the 1 day-old heart possessed an abundance of co-localised P2X2 and P2X5 small receptor clusters on the sarcolemma [26].
• Somatic and axonal effects of ATP via P2X2 but not P2X7 receptors in rat thoracolumbar sympathetic neurones [27].

Analytical, diagnostic and therapeutic context of P2rx2

• In addition, single cell RT-PCR experiments with outer hair cells (OHC) revealed the expression of either the P2X2 or the P2X2-2 splice variant or coexpression of both isoforms in individual cells [16].
• Western blot of whole bladders for P2X2 and P2X3 expression was performed [28].
• Here, we purified the P2X2 receptor using baculovirus-Sf9 cell expression system and observed its structure using electron microscopy [14].
• The FLAG-tagged P2X2 receptor, which has intact ion channel function, was purified to be a single peak by affinity purification and gel filtration chromatography [14].
• 5. Using confocal immunofluorescence, co-localization of P2X2 and P2X3 protein was demonstrated in many petrosal somas and CB afferent terminals in situ [29].

References