Disease relevance of P2rx3

• In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation [1].
• Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice [2].
• Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons [2].
• Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder [2].
• We have isolated a full-length mouse P2X3 gene from a phage lambda-129/Sv genomic library [3].

High impact information on P2rx3

• Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density [2].
• P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons [2].
• The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels [1].
• Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes [2].
• P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin [2].

Biological context of P2rx3

• Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers [1].
• Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit [4].
• These results suggest that cutaneous barrier homeostasis can be regulated by cation flux through a P2X3-like ATP receptor [5].
• Taken together, these data extend our findings for P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder [6].
• RT-PCR analysis of mRNA from intestinal tissues verified P2X3 gene deletion [4].

Anatomical context of P2rx3

• GFP was also expressed in a subpopulation of the primary sensory neurons immunoreactive for the vanilloid receptor TRPV1 and the ATP-gated ion channel P2X3 [7].
• As previously reported, recording from the spinal cord dorsal horn of anesthetized P2X3-/- mice revealed a blunted response of wide dynamic range neurons to hind paw heating [8].
• Afferent cell bodies in thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely labelled from the colon and analysed for P2X3- and TRPV1-like immunoreactivity (LI) [9].
• These data indicate that P2X receptors on sensory and sympathetic ganglion neurones involve almost exclusively P2X2 and P2X3 subunits [6].
• It is concluded that P2X3 subunit-containing receptors participate in neural pathways underlying peristalsis in the mouse intestine in vitro [4].

Associations of P2rx3 with chemical compounds

• ATP, but not alpha,beta-methylene ATP, caused depolarization of AH neurons from P2X3-/- mice [4].
• Topical application of suramin (nonspecific ATP receptor antagonist), pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (P2X receptor antagonist), and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) (P2X1, P2X3, P2X2/3 antagonist) after barrier disruption accelerated the barrier repair [5].
• Peristalsis was inhibited in ileal segments from P2X3-/- mice but longitudinal muscle contractions caused by nicotine and bethanechol were similar in segments from P2X3+/+ and P2X3-/- mice [4].
• This response was completely blocked by intrathecal pretreatment with the non-selective P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and the selective P2X1, P2X3 and P2X2-3 receptor antagonist, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) [10].
• Genetic elimination of ionotropic purinergic receptors (P2X2 and P2X3) eliminates taste responses in the taste nerves, although the nerves remain responsive to touch, temperature, and menthol [11].

Other interactions of P2rx3

• In addition, OSMR-positive neurons decreased, resulting in the reduced number of VR1/P2X3/OSMR-triple positive neurons [12].
• The RAG locus-associated gene T160 is located 1.8 kb upstream of the transcription start site of mouse P2X3 gene [3].
• Using RNase protection and primer extension assays, multiple transcription initiation sites have been mapped in the mouse P2X3 promoter to a region 162-168 bp upstream of the translation initiation codon [3].

Analytical, diagnostic and therapeutic context of P2rx3

• Both reverse transcription polymerase chain reaction assay and immunohistochemical study showed the existence of protein that had a structure similar to P2X3 on hairless mouse epidermis [5].
• Gastrointestinal transit was similar in P2X3+/+ and P2X3-/- mice [4].
• In the present study, we examined the P2X receptors on DRG and nodose neurons from P2X3-deficient (P2X3-/-) mice, using whole cell voltage-clamp recording and immunohistochemistry [13].
• Surface biotinylation showed CGRP augmented P2X3 receptor expression, consistent with confocal microscopy data indicating enhanced P2X3 immunoreactivity beneath the neuronal membrane [14].

References