Mechanisms involved in endothelin‐1‐induced contraction of the pig urinary bladder neck
Loading...
Official URL
Full text at PDC
Publication date
2011
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Citations
Exportar
Citation
Arteaga, J. L., Oresanz Muñoz, L. M., Martínez, M. P. et al. «Mechanisms Involved in Endothelin‐1‐induced Contraction of the Pig Urinary Bladder Neck». Neurourology and Urodynamics, vol. 31, n.o 1, enero de 2012, pp. 156-61. https://doi.org/10.1002/nau.21187.
Abstract
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.