P2Rx3

Official Full Name

purinergic receptor P2X, ligand-gated ion channel, 3

Organism

Mus musculus

GeneID

228139

Background

Enables extracellularly ATP-gated monoatomic cation channel activity. Involved in modulation of chemical synaptic transmission. Acts upstream of or within several processes, including neuromuscular synaptic transmission; response to ATP; and smooth muscle contraction. Located in axon. Is active in Schaffer collateral - CA1 synapse and hippocampal mossy fiber to CA3 synapse. Is expressed in several structures, including branchial arch; embryo ectoderm; gut; nervous system; and retina. Orthologous to human P2RX3 (purinergic receptor P2X 3). [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

P2rx3; P2X3; 4930513E20Rik;

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Detailed Information

P2RX3 gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and may transduce ATP-evoked nociceptor activation. Mouse studies suggest that this receptor is important for peripheral pain responses, and also participates in pathways controlling urinary bladder volume reflexes. The development of selective antagonists for this receptor may have a therapeutic potential in pain relief and the treatment of disorders of urine storage.

P2RX3 associated with pain burden in inflammatory bowel disease of children

A common and burdensome symptom in children of inflammatory bowel disease (IBD) is abdominal pain, which is related to the decline of quality of life. Clinical observation shows that the severity of inflammation is often inconsistent with the degree of abdominal pain, and the pain will continue even if the inflammation is fully treated. These observations indicate that except for inflammation, other mechanisms may mediate pain experience. Victoria et al. collected the clinical data from 29 subjects, including the data from multiple children who were newly diagnosed with IBD. As their analysis showed, pain burden can not be predicted by age, sex, and the degree of rectal inflammation, it is worth noting that the pain burden can be only reflected by the P2rX3 expression from rectal biopsy, which explains approximately 20% of the pain burden variance in the participated patient. Expression of other purinergic receptors, such as P2rX4, P2rX7, and P2rY1, exhibited no obvious relation to pain burden.

P2RX3 associated with traumatic brain injury

Traumatic brain injury (TBI) has emerged as a serious public health problem that is the main cause of severe post-traumatic disability. A large number of studies have shown that differentially expressed genes (DEGs) of neural signaling pathways are closely related to brain injury. Huang et al. explored the gene expression related to neuronal survival in the hippocampus by applying a real-time quantitative polymerase chain reaction. They found the upregulation of gene P2RX3 in rats subjected to TBI based on the Western blot and axon growth assay, and the neurite growth promotion of NG108 cells will happen due to the gene overexpression of P2RX3. All these results demonstrated that P2rx3 and other signaling pathways play a pivotal role in TBI.

The function of P2RX3 in mouse hippocampal neuronal cells

Praja2 (Pja2) is a member of the animal mammalian ring E3 ubiquitin ligase family. It is reported that it not only participates in many types of cancers but also participates in neurological diseases. However, its genetic mechanism in the nervous system is unclear. In order to study the cellular and molecular functions of Pja2 in neuronal cells of mouse hippocampal, Gong et al. tested the regulatory effects of Pja2 on three Alzheimer's disease (AD) genes and cell proliferation by using the HT-22 cells treated with function increase and function loss operation of Pja2. They revealed the regulatory mechanism of the Pja2 gene in the nervous system. Their results suggest that the P2RX3/P2RX7 axis mediated the regulatory function of neuronal cells in mouse hippocampal. The expression of the AD marker gene was inhibited by Pja2, but the axon growth and cell proliferation were promoted by Pja2. In a word, Gong et al. demonstrated that HT-22 cell development and AD marker genes expression was regulated by the inhibition of P2RX3 expression and the promotion of P2RX7 expression.

P2RX3 Figure 1. The illustration of significant genes expressed in the calcium signaling pathway (Gong et al., 2020).

References:

Grossi V, Hyams J S, Young E. P2RX3 Gene Expression is Associated with Pain Burden in Children Newly Diagnosed with Inflammatory Bowel Disease. Gastroenterology, 2017, 152(5): S959.
Huang G H, Cao X Y, Li Y Y, et al. Gene expression profile of the hippocampus of rats subjected to traumatic brain injury. Journal of cellular biochemistry, 2019, 120(9): 15776-15789.
Gong M, Ye S, Li W X, et al. Regulatory function of Praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells. American Journal of Physiology-Cell Physiology, 2020, 318(6): C1123-C1135.

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