%0 Journal Article
%A Arteaga, José Luis
%A Orensanz Muñoz, Luis Miguel
%A Martínez, María Pilar
%A Barahona Gomáriz, María Victoria
%A Recio Visedo, María Paz
%A Martínez Sáenz, Ana
%A Leite Fernandes, Vitor Samuel
%A Fernandes Ribeiro, Ana Sofía
%A García Sacristán, Albino
%A Prieto Ocejo, Dolores
%A Hernández Rodríguez, Medardo Vicente
%T Mechanisms involved in endothelin‐1‐induced contraction of the pig urinary bladder neck
%D 2011
%@ 0733-2467
%U https://hdl.handle.net/20.500.14352/94072
%X Aims: There is no information about the signaling pathways involved in the endothelin-1 (ET-1)-induced contraction of bladder neck. The current study investigates the mechanisms involved in the ET-1-elicited contraction in the pig bladder neck. Methods: Bladder neck strips were mounted in organ baths containing physiological saline solution at 378C and gassed with 95% O2 and 5% CO2, for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ETA receptor expression was also determined, by both immunohistochemistry and Western blot. Results: ETA receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ETA-immunoreactivity (ETA-IR) was identified within nerve fibers among smooth muscle bundles. ET-1 and ET-2 evoked similar concentration-dependent contractions of urothelium-denuded preparations. ET-3 produced a slight response, whereas the ETB receptor agonist BQ3020 failed to promote contraction. BMS182874, an ETA receptor antagonist, reduced ET-1-induced contraction whereas BQ788, an ETB antagonist, did not change such responses. ET-1 contractions were reduced by extracellular Ca2þ removal and by inhibition of voltage-gated Ca2þ (VOC) (L-type) and non-VOC channels, Rho/Rho-kinase pathway, and neuronal VOC channels. NA produced contractions which were enhanced by ET-1 threshold concentrations. ETA receptor blockade enhanced nitric oxide-dependent nerve-mediated relaxations. Conclusions: These results suggest that ET-1 produces contraction via muscular ETA receptors coupled to extracellular Ca2þ entry via VOC (L-type) and non-VOC channels. Intracellular Ca2þ mobilization and a Rho/Rho-kinase pathway could also be involved in these responses. ET-1-evoked potentiation on noradrenergic contraction, and neuronal ETA receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated. Neurourol. Urodynam. 31:156–161, 2012. 
 2011 Wiley Periodicals, Inc.
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