title: Role of calcitonin gene-related peptide in inhibitory neurotransmission to the pig bladder neck.
abstract: OBJECTIVE
  We studied the role of calcitonin gene-related peptide in nonadrenergic, noncholinergic neurotransmission to the pig bladder neck.
  
  
  METHODS
  We used immunohistochemical techniques to determine the distribution of calcitonin gene-related peptide immunoreactive fibers as well as organ baths for isometric force recording. We investigated relaxation due to endogenously released or exogenously applied calcitonin gene-related peptide in urothelium denuded phenylephrine precontracted strips treated with guanethidine, atropine and NG-nitro-L-arginine to block noradrenergic neurotransmission, muscarinic receptors and nitric oxide synthase, respectively.
  
  
  RESULTS
  Rich calcitonin gene-related peptide immunoreactive innervation was found penetrating through the adventitia and distributed in the suburothelial and muscle layers. Numerous, variable size, varicose calcitonin gene-related peptide immunopositive terminals were seen close below the urothelium. In the muscle layer calcitonin gene-related peptide immunopositive nerves usually appeared as varicose terminals running along muscle fibers. Electrical field stimulation (2 to 16 Hz) and exogenous calcitonin gene-related peptide (0.1 nM to 0.3 μM) evoked frequency and concentration dependent relaxation, respectively. Nerve responses were potentiated by capsaicin, decreased by calcitonin gene-related peptide (8-37) and abolished by tetrodotoxin, capsaicin sensitive primary afferent blockers, calcitonin gene-related peptide receptors and neuronal voltage gated Na+ channels. Calcitonin gene-related peptide-induced relaxation was potentiated by the neuronal voltage gated Ca2+ channels blocker ω-conotoxin-GVIA and decreased by calcitonin gene-related peptide (8-37). Calcitonin gene-related peptide relaxation was not modified by blockade of endopeptidases, nitric oxide synthase, guanylyl cyclase and cyclooxygenase.
  
  
  CONCLUSIONS
  Results suggest that calcitonin gene-related peptide is involved in the nonadrenergic, noncholinergic inhibitory neurotransmission of the pig bladder neck, producing relaxation through neuronal and muscle calcitonin gene-related peptide receptors. Nitric oxide/cyclic guanosine monophosphate and cyclooxygenase pathways do not seem to be involved in such responses.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, and Departamento de Investigación, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-Sáenz
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Luis M
authors.initials: LM
authors.lastname: Orensanz
authors.forename: Vítor S
authors.initials: VS
authors.lastname: Fernandes
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.forename: Joaquín
authors.initials: J
authors.lastname: Carballido
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; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D005260:Female; D008297:Male; D013552:Swine; D009435:Synaptic Transmission; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology*
chemical_list: D015740:Calcitonin Gene-Related Peptide