{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:49:31Z","timestamp":1788385771201,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T00:00:00Z","timestamp":1681516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK 119482"],"award-info":[{"award-number":["DK 119482"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The urinary bladder requires adequate concentrations of extracellular adenosine 5\u2032-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium\/lamina propria (LP) in a mechanosensitive manner. Using 1,N6-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and \u03c9-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling.<\/jats:p>","DOI":"10.3390\/ijms24087322","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T03:14:09Z","timestamp":1681701249000},"page":"7322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5210-9137","authenticated-orcid":false,"given":"Mafalda S. L.","family":"Aresta Branco","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Gutierrez Cruz","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Borhani Peikani","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-3323","authenticated-orcid":false,"given":"Violeta N.","family":"Mutafova-Yambolieva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11302-013-9395-y","article-title":"Purinergic signalling in the urinary tract in health and disease","volume":"10","author":"Burnstock","year":"2014","journal-title":"Purinergic Signal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1469-7793.1997.503bb.x","article-title":"ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes\u2014A possible sensory mechanism?","volume":"505","author":"Ferguson","year":"1997","journal-title":"J. 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