Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission

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dc.contributor.authorAgis Torres, Ángel
dc.contributor.authorRecio Visedo, María Paz
dc.contributor.authorLópez-Oliva Muñoz, María Elvira
dc.contributor.authorMartínez Sainz, María Del Pilar
dc.contributor.authorBarahona Gomáriz, María Victoria
dc.contributor.authorBenedito Castellote, Sara
dc.contributor.authorBustamante, Salvador
dc.contributor.authorJiménez-Cidre; Miguel Ángel
dc.contributor.authorGarcía Sacristán, Albino
dc.contributor.authorPrieto Ocejo, Dolores
dc.contributor.authorLeite Fernandes, Vitor Samuel
dc.contributor.authorHernández Rodríguez, Medardo Vicente
dc.date.accessioned2023-12-28T10:44:49Z
dc.date.available2023-12-28T10:44:49Z
dc.date.issued2018-03-16
dc.description.abstractNitric oxide (NO) and hydrogen sulfide (H2S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H2S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H2S generation was diminished by H2S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H2S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H2S-mediated inhibitory neurotransmission.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Veterinaria
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationAgis-Torres, Á., Recio, P., López-Oliva, M.E. et al. Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission. Sci Rep 8, 4711 (2018). https://doi.org/10.1038/s41598-018-22934-1
dc.identifier.doi10.1038/s41598-018-22934-1
dc.identifier.essn2045-2322
dc.identifier.officialurlhttps://www.nature.com/articles/s41598-018-22934-1#rightslink
dc.identifier.urihttps://hdl.handle.net/20.500.14352/91743
dc.journal.titleScientific Reports
dc.language.isoeng
dc.page.initial4711
dc.publisherNature Research
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu616.61/.63
dc.subject.keywordBladder
dc.subject.keywordInhibition
dc.subject.ucmFarmacología (Farmacia)
dc.subject.unesco3207 Patología
dc.titlePhosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number8
dspace.entity.typePublication
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