Activation of P2Y 6 Receptors Facilitates Nonneuronal Adenosine Triphosphate and Acetylcholine Release from Urothelium with the Lamina Propria of Men with Bladder Outlet Obstruction
2015; Lippincott Williams & Wilkins; Volume: 194; Issue: 4 Linguagem: Inglês
10.1016/j.juro.2015.05.080
ISSN1527-3792
AutoresIsabel Silva, Fátima Ferreirinha, M.T. Magalhães‐Cardoso, Miguel Silva‐Ramos, Paulo Correia‐de‐Sá,
Tópico(s)Sexual function and dysfunction studies
ResumoNo AccessJournal of UrologyInvestigative Urology1 Oct 2015Activation of P2Y6 Receptors Facilitates Nonneuronal Adenosine Triphosphate and Acetylcholine Release from Urothelium with the Lamina Propria of Men with Bladder Outlet Obstruction Isabel Silva, Fátima Ferreirinha, Maria Teresa Magalhães-Cardoso, Miguel Silva-Ramos, and Paulo Correia-de-Sá Isabel SilvaIsabel Silva Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal , Fátima FerreirinhaFátima Ferreirinha Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal , Maria Teresa Magalhães-CardosoMaria Teresa Magalhães-Cardoso Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal , Miguel Silva-RamosMiguel Silva-Ramos Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto and Serviço de Urologia, Centro Hospitalar do Porto, Porto, Portugal , and Paulo Correia-de-SáPaulo Correia-de-Sá Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal View All Author Informationhttps://doi.org/10.1016/j.juro.2015.05.080AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of uridine diphosphate sensitive P2Y6 receptors increases voiding frequency in rats indirectly by releasing adenosine triphosphate from the urothelium. To our knowledge this mechanism has never been tested in the human bladder. Materials and Methods: We examined the role of the uridine diphosphate sensitive P2Y6 receptor on tetrodotoxin insensitive nonneuronal adenosine triphosphate and [3H]acetylcholine release from the human urothelium with the lamina propria of control organ donors and patients with benign prostatic hyperplasia. Results: The adenosine triphosphate-to-[3H]acetylcholine ratio was fivefold higher in mucosal urothelium/lamina propria strips from benign prostatic hyperplasia patients than control men. The selective P2Y6 receptor agonist PSB0474 (100 nM) augmented by a similar amount adenosine triphosphate and [3H]acetylcholine release from mucosal urothelium/lamina propria strips from both groups of individuals. The facilitatory effect of PSB0474 was prevented by MRS2578 (50 nM) and by carbenoxolone (10 μM), which block P2Y6 receptor and pannexin-1 hemichannels, respectively. Blockade of P2X3 (and/or P2X2/3) receptors with A317491 (100 nM) also attenuated release facilitation by PSB0474 in control men but not in patients with benign prostatic hyperplasia. Immunolocalization studies showed that P2Y6, P2X2 and P2X3 receptors were present in choline acetyltransferase positive urothelial cells. In contrast to P2Y6 staining, choline acetyltransferase, P2X2 and P2X3 immunoreactivity decreased in the urothelium of benign prostatic hyperplasia patients. Conclusions: Activation of P2Y6 receptor amplifies mucosal adenosine triphosphate release underlying bladder overactivity in patients with benign prostatic hyperplasia. Therefore, we propose selective P2Y6 receptor blockade as a novel therapeutic strategy to control persistent storage symptoms in obstructed patients. 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Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 194Issue 4October 2015Page: 1146-1154Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordsacetylcholineadenosine triphosphateurinary bladder neck obstructionpurinoceptor P2Y6urotheliumAcknowledgmentsHelena Costa e Silva and Belmira Silva provided technical assistance.MetricsAuthor Information Isabel Silva Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal More articles by this author Fátima Ferreirinha Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal More articles by this author Maria Teresa Magalhães-Cardoso Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal More articles by this author Miguel Silva-Ramos Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto and Serviço de Urologia, Centro Hospitalar do Porto, Porto, Portugal More articles by this author Paulo Correia-de-Sá Laboratório de Farmacologia e Neurobiologia, Porto, Portugal Center for Drug Discovery and Innovative Medicines, Porto, Portugal More articles by this author Expand All Advertisement PDF downloadLoading ...
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