Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/122249
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Type: | Journal article |
Title: | Purinergic receptor mediated calcium signalling in urothelial cells |
Author: | Chess-Williams, R. Sellers, D.J. Brierley, S.M. Grundy, D. Grundy, L. |
Citation: | Scientific Reports, 2019; 9(1):16101-1-16101-10 |
Publisher: | Nature Publishing Group |
Issue Date: | 2019 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | Russell Chess-Williams, Donna J. Sellers, Stuart M. Brierley, David Grundy, Luke Grundy |
Abstract: | Non-neuronal ATP released from the urothelium in response to bladder stretch is a key modulator of bladder mechanosensation. Whilst non-neuronal ATP acts on the underlying bladder afferent nerves to facilitate sensation, there is also the potential for ATP to act in an autocrine manner, modulating urothelial cell function. The aim of this study was to systematically characterise the functional response of primary mouse urothelial cells (PMUCs) to ATP. PMUCs isolated from male mice (14-16 weeks) were used for live-cell fluorescent calcium imaging and qRT-PCR to determine the expression profile of P2X and P2Y receptors. The majority of PMUCs (74-92%) responded to ATP (1 μM-1 mM), as indicted by an increase in intracellular calcium (iCa2+). PMUCs exhibited dose-dependent responses to ATP (10 nM-1 mM) in both calcium containing (2 mM, EC50 = 3.49 ± 0.77 μM) or calcium free (0 mM, EC50 = 9.5 ± 1.5 μM) buffers. However, maximum iCa2+ responses to ATP were significantly attenuated upon repetitive applications in calcium containing but not in calcium free buffer. qRT-PCR revealed expression of P2X1-6, and P2Y1-2, P2Y4, P2Y6, P2Y11-14, but not P2X7 in PMUCs. These findings suggest the major component of ATP induced increases in iCa2+ are mediated via the liberation of calcium from intracellular stores, implicating functional P2Y receptors that are ubiquitously expressed on PMUCs. |
Keywords: | Urothelium Epithelial Cells Animals Mice, Inbred C57BL Mice Calcium Adenosine Triphosphate Calcium Signaling Male Receptors, Purinergic P2X Receptors, Purinergic P2Y |
Rights: | © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-019-52531-9 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1140297 http://purl.org/au-research/grants/nhmrc/1139366 http://purl.org/au-research/grants/nhmrc/1126378 |
Published version: | http://dx.doi.org/10.1038/s41598-019-52531-9 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_122249.pdf | Published version | 1.1 MB | Adobe PDF | View/Open |
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