title: Endothelin ET(B) receptors are involved in the relaxation to the pig urinary bladder neck.
abstract: OBJECTIVE
  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 ET(B) receptors involved in the relaxation of pig bladder neck.
  
  
  METHODS
  ET(B) receptor expression was determined by immunohistochemistry and urothelium-denuded bladder neck strips were mounted in organ baths for isometric force recording.
  
  
  RESULTS
  ET(B) -immunoreactivity (ET(B) -IR) was observed within nerve fibers among smooth muscle bundles and urothelium. BQ3020 (0.01-300 nM), an ET(B) receptor agonist, produced concentration-dependent relaxations which were reduced by BQ788, an ET(B) receptor antagonist, and by inhibitors of protein kinase A (PKA) and large (BK(Ca) )- or small (SK(Ca) )-conductance Ca(2+) -activated K(+) channels. Pretreatment with BK(Ca) or SK(Ca) channel inhibitors plus PKA blocking did not cause further inhibition compared with that exerted by inhibiting BK(Ca) or SK(Ca) channels only. BQ3020-induced relaxation was not modified by blockade of either nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX) or of intermediate-conductance Ca(2+) -activated-(IK(Ca) ), ATP-dependent-(K(ATP) ), or voltage-gated-(K(v) ) 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 ET(B) receptors, NO/cGMP- and COX-independent-, cAMP-PKA pathway-dependent-mechanisms, and involving BK(Ca) and SK(Ca) channel activation. ET(B) receptors are also involved in the NANC inhibitory neurotransmission.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Arteaga
authors.forename: Luis M
authors.initials: LM
authors.lastname: Orensanz
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Barahona
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-Sáenz
authors.forename: Vítor S
authors.initials: VS
authors.lastname: Fernandes
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.forename: Joaquín
authors.initials: J
authors.lastname: Carballido
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
chemical_list: D016232:Endothelins; D004791:Enzyme Inhibitors; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D026902:Potassium Channel Blockers; D044023:Receptor, Endothelin B; D018160:Receptors, Cytoplasmic and Nuclear; D051640:Small-Conductance Calcium-Activated Potassium Channels; C075771:BQ 3020; D009569:Nitric Oxide; C086539:BQ 788; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP