Disease relevance of P2RX2

• Furthermore, H2O2 attenuated the effect of hypoxia on homomeric P2X2 whole-cell currents [1].
• Baculovirus expression provides direct evidence for heteromeric assembly of P2X2 and P2X3 receptors [2].
• The 5' untranslated leader sequence from the encephalomyocarditis virus was used to engineer bicistronic or tricistronic expression vectors encoding two subunits (P2X2 and P2X3) of an ATP-gated cation channel [3].
• A-317491 also blocked native P2X3 and P2X2/3 receptors in rat dorsal root ganglion neurons [4].
• In rat pheochromocytoma PC-12 cells, treatment with 9-cis-retinoic acid as well as all-trans-retinoic acid significantly increased the mRNA and protein level of P2X2 receptor [5].

High impact information on P2RX2

• Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons [6].
• Brief (< 1 s) applications of ATP to nodose ganglion neurons or to cells transfected with P2X2 or P2X4 receptor cDNAs induce the opening of a channel selectively permeable to small cations within milliseconds [7].
• This effect is enhanced in P2X2 receptors carrying point mutations in the second transmembrane segment [7].
• In all of the cell lines tested, P2-purinergic receptor agonists, including ATP and certain hydrolysis-resistant adenine nucleotides, induced a rapid, transient increase in cytoplasmic free Ca2+ that was detectable at 50 to 100 nM ATP, was maximal at 100 microM ATP, and was inhibited approximately 50% by chelation of extracellular Ca2+ [8].
• P2-purinergic receptor agonists inhibit the growth of androgen-independent prostate carcinoma cells [8].

Biological context of P2RX2

• Inhibitors of the mitochondrial electron transport chain that reduce (rotenone and myxothiazol) or increase (antimycin A) the production of ROS altered the magnitude of P2X2-mediated currents [1].
• 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 [4].
• When this region is removed, or when charge is added to it, P2X6 forms homotrimeric assemblies, undergoes complex glycosylation and is delivered to the plasma membrane, albeit less efficiently than the P2X2 receptor [9].
• When alpha,beta-methylene ATP was the agonist (activating heteromeric P2X2/3 receptors), the inhibition by TNP-ATP conformed to a single binding site (half-maximal concentration about 3 nM) [10].
• P2X2 expression was found in nuclei of rat facial motoneurons, with nuclear export in the cytoplasm after nerve resection [11].

Anatomical context of P2RX2

• Human, rat, and mouse testicular smooth muscle demonstrated purinergic responsiveness, probably mediated through the P2X1 and/or P2X2 receptors [12].
• In RT-PCR, circular myocytes expressed mRNAs encoding P2X2, 3 and 4, while longitudinal myocytes expressed mRNAs for P2X3 and 5 [13].
• Labelling for each P2X subtype was seen in the apical, lateral and basal compartments on Days 1 and 3, except for P2X2 which was only observed in the basement membrane [14].
• We also show a physical interaction between P2X2 and rho1 receptors expressed in oocytes and the co-clustering of these receptors in transfected hippocampal neurons [15].
• Human erythrocytes expressed P2X7 receptors on all cells examined from eight of eight subjects, as well as P2X2 at a far lower staining intensity in six of eight subjects [16].

Associations of P2RX2 with chemical compounds

• Co-expression with P2X2 induces retargeting and recruitment of mainly intracellular rho1/GABA receptors to surface clusters [15].
• The relative permeabilities (PX/PNa) were 2.3, 1.0, 1.0, 0.95, 0.72, 0.5, 0.29, 0.16, 0.04 and 0.03 for guanidinium, potassium, sodium, methylamine, caesium, dimethylamine, 2-methylethanolamine, tris(hydroxymethyl)-aminomethane, tetraethylammonium and N-methyl-D-glucamine, respectively (values for P2X2 receptor) [17].
• 4. Affinity estimates of 15 other nucleotide analogues for the [35S]-ATP gamma S binding sites on the two recombinant P2X purinoceptor subtypes were surprisingly similar (less than 5 fold difference), the only exception being 2'-deoxy ATP which possessed 8 fold higher affinity for rat P2X2 than for human P2X1 purinoceptors [18].
• Positive immunostaining was detected in NEB cells using double-label immunohistochemistry with antibodies against P2X2 and P2X3 receptor subunits, which co-localized with serotonin (5-HT), a marker of NEB cells [19].
• P2X2 receptor subunits are localized to the luminal membranes of epithelial cells and hair cells lining scala media [20].

Other interactions of P2RX2

• 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].
• In contrast, in the solitary tract and its nucleus (NTS), colocalization of P2X2- and P2X3-ir was seen at low and high magnification [22].

Analytical, diagnostic and therapeutic context of P2RX2

• Atomic force microscopy imaging demonstrates that P2X2 receptors are trimers but that P2X6 receptor subunits do not oligomerize [23].
• In cells expressing homomeric P2X2 receptors, perfusion of 5 microM ATP (EC25) induced an inward whole-cell current that showed little desensitization during repeated exposures under continuously normoxic conditions [1].
• 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 [2].
• Involvement of P2X1 and P2X2 purinergic receptors in motoneuron response to injury was investigated with Western blotting and immunohistochemistry and correlated with motoneuron loss, Bcl-2 expression, nitric oxide synthase induction and glial activation [11].
• Furthermore, this paper demonstrates the role of quantitative structure-activity relationships (QSARs) in P2X research (calcium ion permeability of the wild-type and after site-directed mutagenesis of the rat P2X2 receptor protein, KN-62 analogs as competitive antagonists of the human P2X7 receptor) [24].

References