Disease relevance of P2RX3

• This study examined the effect of acute hypoxia on cloned homo- and heteromeric P2X2 and P2X3 receptors expressed in human embryonic kidney 293 cells [1].
• Within a large proportion of dorsal root ganglion neurons and the terminals of their axons, VR1-ir was colocalized with staining for the P2X3 purinoceptor, and with binding sites for the lectin IB4 [2].
• P2X3 may represent a selective therapeutic target for other causes of overactive bladder [3].
• Baculovirus expression provides direct evidence for heteromeric assembly of P2X2 and P2X3 receptors [4].
• Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis [5].

High impact information on P2RX3

• Some agonists (e.g., alphabeta-methylene ATP) and antagonists [e.g., 2',3'-O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3 subunits [6].
• Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory neurons express messenger RNA for the P2X3 receptor [7].
• Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings and cell bodies [7].
• Stretch receptors had currents that differed from those of P2X3 channels, and had no P2X3 immunoreactivity [7].
• Here we report the cloning of a complementary DNA (P2X3) from rat dorsal root ganglia that had properties dissimilar to those of sensory neurons [8].

Chemical compound and disease context of P2RX3

• 9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- mice, whereas basal thermal and mechanical pain sensitivity is unchanged [9].
• Effective agents for sarcoidosis such as tranilast, allopurinol, and captopril inhibited in vitro MGC formation through inhibiting the expression of adhesion molecule and purinergic receptor [10].

Biological context of P2RX3

• The full-length cDNA encodes a protein 397 amino acids long which shows a high amino-acid sequence identity with the rat P2X3 purinoceptor (93%) [11].
• Tissue distribution analysis of human P2X3 receptor mRNA shows a restricted expression pattern, i.e. transcripts are limited to the spinal cord and heart [11].
• By fluorescence in situ hybridization, the human P2X3 gene has been mapped to region q12 of chromosome 11 [11].
• A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 microM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes [12].
• The efficiency of expression was improved by co-transfection with P2X2 and P2X3, when compared to transfection with the P2X3 subtype alone [13].

Anatomical context of P2RX3

• Weaker P2X3-like immunoreactivity was also detected in fewer nerve fibers [14].
• B lymphocytes are known to synthesise the P2X7 subtype of the P2X purinergic receptor family; however, the identification of the other six P2X subtypes on these cells has been limited by the absence of specific antibodies [15].
• In RT-PCR, circular myocytes expressed mRNAs encoding P2X2, 3 and 4, while longitudinal myocytes expressed mRNAs for P2X3 and 5 [16].
• However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor immunoreactivity on the smooth muscle cells [17].
• Heterologous expression of human P2X3 cRNA in Xenopus oocytes generates a fast desensitizing ATP-activated channel with pharmacological properties resembling the profile of the rat homologue receptor [11].

Associations of P2RX3 with chemical compounds

• AIMS: To investigate the levels of the capsaicin or vanilloid receptor-1 (VR1) and the ATP-gated purinoceptor P2X3 in painful and nonpainful human tooth pulps [14].
• Moreover, ATP-evoked currents on human P2X3 receptor are efficiently blocked in a reversible manner by the purinoceptor antagonists, suramin and PPADS [11].
• Here, we show that intracellular Ca2+ mobilization via the purinergic receptor agonist ATP, the muscarinic receptor agonist carbachol or the Ca(2+)-ATPase inhibitor thapsigargin leads to formation of anandamide, and subsequent TRPV1-dependent Ca2+ influx in transfected cells and sensory neurons of rat dorsal root ganglia (DRG) [18].
• To better characterize the release pathway(s) for IL-1beta and IL-18 we evaluated the role of lipopolysaccharide priming, of interleukin-1beta-converting enzyme (ICE) inhibition, of human purinergic receptor (P2X(7)) function, and of signaling pathways in human monocytes induced by ATP [19].
• Following hints in the early literature about adenosine 5'-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves [20].

Other interactions of P2RX3

• Each member of the family can form functional homomeric channels, but only P2X2 and P2X3 have been shown to combine to form a unique heteromeric channel [21].
• Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp [14].
• In OSM-deficient mice, TRPV1/P2X3/OSMRbeta triple-positive neurons were significantly decreased [22].
• RESULTS: The mRNA transcripts of most P2 receptors were detected in primary B cells; the expression of P2X3 and P2X7 receptors was the lowest of all the P2 receptors [23].
• Absence of the responses of alphabeta-methylene ATP and 2-methylthio-ATP excluded functionally active P2X3, P2X4, and P2Y1 receptors as far as [Ca2+]i increase is concerned [24].

Analytical, diagnostic and therapeutic context of P2RX3

• Whole-cell recordings from these cells showed that ATP and alphabetamethylene-ATP evoked currents with agonist sensitivity and desensitization quite distinct from those observed when P2X2 or P2X3 receptors were expressed alone [4].
• TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics [25].
• Using relative densitometry units normalized for actin expression in the Western blots stretch of IC BUCs resulted in 66% more expression of P2X3 than any other experimental condition (p = 0.003) [5].
• To confirm P2X3 expression in a whole cell preparation flow cytometry and fluorescence activated cell sorter analysis were used [5].
• Cells were harvested at various times, and immunofluorescence and Western blots were performed for P2X3 expression [5].

References