RT Journal Article
T1 Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission
A1 Agis Torres, Ángel
A1 Recio Visedo, María Paz
A1 López-Oliva Muñoz, María Elvira
A1 Martínez Sainz, María Del Pilar
A1 Barahona Gomáriz, María Victoria
A1 Benedito Castellote, Sara
A1 Bustamante, Salvador
A1 Jiménez-Cidre; Miguel Ángel, 
A1 García Sacristán, Albino
A1 Prieto Ocejo, Dolores
A1 Leite Fernandes, Vitor Samuel
A1 Hernández Rodríguez, Medardo Vicente
AB Nitric 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.
PB Nature Research
YR 2018
FD 2018-03-16
LK https://hdl.handle.net/20.500.14352/91743
UL https://hdl.handle.net/20.500.14352/91743
LA eng
NO Agis-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
DS Docta Complutense
RD 26 ago 2024