Disease relevance of P2rx3

• We found that endogenously active CaMKII up-regulates basal P2X3 receptor activity in dorsal root ganglion neurons [1].
• Furthermore, P2X3 localizes in raft-containing fractions in transiently transfected SH-SY5Y neuroblastoma cells [2].
• Its efficacy demonstrates the importance of peripheral P2X3/P2X(2/3) receptors in mediating ATP-associated mechanical hyperalgesia following inflammation, confirming previous suggestions of a significant role for P2X(2/3) [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].
• Thus, it is suggested that the activation of the P2X3 receptor is involved in the phosphorylation of ERK in DRG neurons and the mechanical hypersensitivity of the inflamed knee joint [5].

Psychiatry related information on P2rx3

• P2X3 receptor blockade raised the pressure and volume thresholds for the reflex, whereas P2X1 receptor blockade diminished motor activity associated with voiding [6].

High impact information on P2rx3

• P2X3 is the only ligand-gated channel known to be expressed exclusively by a subset of sensory neurons [7].
• In contrast, P2X3 mRNA is localized to small-fiber sensory neurons and produces less mechanosensitivity in oocytes [8].
• Sensory neurons of the trigeminal, dorsal root, and nodose ganglia express all six RNAs; P2X3 is found only there [9].
• The spinal cord expresses all receptors except P2X3 [9].
• The suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic acid groups [10].

Chemical compound and disease context of P2rx3

• Whole-cell patch-clamp recordings from cultured rat dorsal root ganglion neurons demonstrated that the P2Y1 receptor agonists adenosine 5'-O-2-thiodiphosphate (ADP-beta-S) and 2-methylthio adenosine 5'-diphosphate (2-MeSADP) inhibit the alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP)-induced P2X3 receptor-currents [11].

Biological context of P2rx3

• IP5I blocked alphabeta-methylene ATP (alphabeta-meATP)-evoked P2X3 responses in a concentration-dependent manner (IC50 = 0.6 +/- 0.1 microM) [12].
• These results suggest that TNP-ATP acts as a competitive antagonist and competes with alphabeta-meATP at the P2X3 agonist binding site [12].
• Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus [13].
• Heterogeneity in ATP current kinetics occurs even though immunocytochemical staining reveals a relatively homogeneous and widespread expression of the P2X2 and P2X3 subunits [14].
• Using inactivation protocols, we demonstrate the presence of homomeric P2X3-like receptors and non-inactivating P2X receptors, which indicates that individual subsets of adult dorsal root ganglion neurons have distinct P2X receptor phenotypes, and that individual DRG neurons may express multiple P2X receptor subtypes [15].

Anatomical context of P2rx3

• We provide direct biochemical evidence that P2X3 receptor localizes into lipid rafts, in primary cultures of cerebellar granule neurons as well as in brain and dorsal root ganglia extracts [2].
• Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea [16].
• Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X1 and P2X3 receptors [17].
• These studies demonstrate plastic expression of P2X2 and P2X3 receptors in bladder and spinal cord during early postnatal development at times coincident with appearance of mature voiding patterns [18].
• Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach [19].

Associations of P2rx3 with chemical compounds

• The former effect was mimicked by a P2X3 agonist, alpha,beta-methylene ATP, at 10(-5) M, while the latter was mimicked by 2-methylthio ADP (a P2Y1 agonist) or UTP (a P2Y2 agonist) at 10(-3) M, suggesting that the former is mediated by P2X receptors and the latter by P2Y receptors [20].
• Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization [21].
• 5. These results suggest that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3 [22].
• 3 Phenol red (a P2X1/P2X3 antagonist; 0.1 and 1 micromol kg(-1)) caused a significant increase in the pressure and volume thresholds required to initiate a reflex and, at the higher dose, also caused a reduction in postinfusion isovolumetric contractions [6].
• 5 It is concluded that P2X1 and P2X3 receptors play a fundamental role in the micturition reflex in urethane-anesthetized female rats [6].

Co-localisations of P2rx3

• Both P2X2 and P2X3 receptor immunoreactivities were highly co-localized with calretinin positive IGLEs as shown by confocal laser scanning microscopy [23].

Regulatory relationships of P2rx3

• 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].
• Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons [11].
• About 80% of the neurons with P2X3 receptor immunoreactivity in the myenteric plexus and about 40% in the submucosal plexus expressed calretinin [24].
• Approximately 30-75% of the neurons with P2X3 receptor immunoreactivity in the submucosal plexus expressed calbindin, while none of them were found to express calbindin in the myenteric plexus [24].
• P2X3 receptors are down-regulated after peripheral nerve injury and their expression can be regulated by glial cell-derived neurotrophic factor [25].

Other interactions of P2rx3

• Western blot demonstrated an age-dependent decrease (R(2) = 0.96, P </= 0.005) in P2X2 receptor expression in bladder, whereas P2X3 receptor expression in bladder peaked (P </= 0.005) during P14-P21 [18].
• The presence of other ATP receptors such P2Y1 or P2X2/P2X3 heteropolymers in a small fraction of the cells cannot be excluded [26].
• P2X1,2 and 4 receptors were detected in vascular smooth muscle, while P2X3 receptors appeared to be associated with endothelial cells; some small arteries were positive for P2X5, possibly labelling vascular smooth muscle or fibroblasts in the adventitia [27].
• 3. In situ hybridization histochemistry for P2X3 and P2X4 receptor mRNAs showed that both mRNAs were expressed throughout the SON and in the paraventricular nucleus (PVN) [28].
• This study reports the presence of functional P2X3 and P2X7 receptors at synaptic sites, which provides complexity and regulatory possibilities to the cerebellar neurotransmission [29].

Analytical, diagnostic and therapeutic context of P2rx3

• Here we report the molecular cloning and characterization of a new member of the P2X receptor family, P2X3, expressed by these cells [7].
• Western analyses indicate that electrical stimulation enhances the expression of P2X3 receptors in the membrane and that the enhancement is blocked by the inhibitor [1].
• We studied the activity of the noncompetitive antagonist P1, P5-di[inosine-5'] pentaphosphate (IP5I) at the P2X3 receptor, compared with the well studied competitive antagonist TNP-ATP, using a whole-cell voltage-clamp technique in dissociated rat DRG neurons [12].
• Western blot of whole bladders for P2X2 and P2X3 expression was performed [18].
• 5. Using confocal immunofluorescence, co-localization of P2X2 and P2X3 protein was demonstrated in many petrosal somas and CB afferent terminals in situ [30].

References