Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

Xiao-Fei Gao, Ji-Feng Feng, Wei Wang, Zheng-Hua Xiang, Xiu-Jie Liu, Chan Zhu, Zong-Xiang Tang, Xin-Zhong Dong and Cheng He ()
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Xiao-Fei Gao: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University
Ji-Feng Feng: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University
Wei Wang: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University
Zheng-Hua Xiang: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University
Xiu-Jie Liu: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University
Chan Zhu: Nanjing University of Chinese Medicine
Zong-Xiang Tang: Nanjing University of Chinese Medicine
Xin-Zhong Dong: Center for Sensory Biology, School of Medicine, Johns Hopkins University
Cheng He: Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Pirt is a transmembrane protein predominantly expressed in peripheral neurons. However, the physiological and pathological roles of Pirt in hollow viscus are largely unknown. Here we show that Pirt deficiency in mice causes bladder overactivity. The density of α,β-meATP-induced currents is significantly reinforced in Pirt-deficient dorsal root ganglion (DRG) neurons. Pirt and P2X3 receptor co-localize in bladder nerve fibres and heterologous Pirt expression significantly reduces P2X3-mediated currents. Pirt interacts with P2X3 through the N-terminal 14 amino-acid residues. TAT-conjugated PirtN14 peptide (PirtN14) is sufficient to inhibit P2X3 activation in bladder DRG neurons and to alleviate bladder overactivity in Pirt−/− mice. Pirt expression is decreased in the bladder of cyclophosphamide (CYP)-treated mice, a commonly used model of bladder overactivity. Importantly, PirtN14 administration reduces the frequency of bladder voiding and restores the voided volume of CYP-treated mice. Therefore, our results demonstrate that Pirt is an endogenous regulator of P2X3 in bladder function.

Date: 2015
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DOI: 10.1038/ncomms8650

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