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- Title
Endothelin ET<sub>B</sub> Receptors Are Involved in the Relaxation to the Pig Urinary Bladder neck.
- Authors
Arteaga, José Luis; Orensanz, Luis M.; Martínez, María Pilar; Barahona, María Victoria; Martínez-Sáenz, Ana; Fernandes, Vítor S.; Bustamante, Salvador; Carballido, Joaquín; Benedito, Sara; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo
- Abstract
Aims The involvement of endothelin receptors in the contraction of the lower urinary tract smooth muscle is well established. There is scarce information, however, about endothelin receptors mediating relaxation of the bladder outlet region. The current study investigates the possible existence of endothelin ETB receptors involved in the relaxation of pig bladder neck. Methods ETB receptor expression was determined by immunohistochemistry and urothelium-denuded bladder neck strips were mounted in organ baths for isometric force recording. Results ETB-immunoreactivity (ETB-IR) was observed within nerve fibers among smooth muscle bundles and urothelium. BQ3020 (0.01-300 nM), an ETB receptor agonist, produced concentration-dependent relaxations which were reduced by BQ788, an ETB receptor antagonist, and by inhibitors of protein kinase A (PKA) and large (BKCa)- or small (SKCa)-conductance Ca2+-activated K+ channels. Pretreatment with BKCa or SKCa channel inhibitors plus PKA blocking did not cause further inhibition compared with that exerted by inhibiting BKCa or SKCa channels only. BQ3020-induced relaxation was not modified by blockade of either nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX) or of intermediate-conductance Ca2+-activated-(IKCa), ATP-dependent-(KATP), or voltage-gated-(Kv) K+ channels. Under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation (0.5-16 Hz) evoked frequency-dependent relaxations, which were reduced by BQ788 and potentiated by threshold concentrations of BQ3020. Conclusions These results suggest that BQ3020 produces relaxation of the pig bladder neck via activation of muscle endothelin ETB receptors, NO/cGMP- and COX-independent-, cAMP-PKA pathway-dependent-mechanisms, and involving BKCa and SKCa channel activation. ETB receptors are also involved in the NANC inhibitory neurotransmission. Neurourol. Urodynam. 31:688-694, 2012. © 2012 Wiley Periodicals, Inc.
- Publication
Neurourology & Urodynamics, 2012, Vol 31, Issue 5, p688
- ISSN
0733-2467
- Publication type
Article
- DOI
10.1002/nau.22203