Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling

J Urol. 2013 Aug;190(2):746-56. doi: 10.1016/j.juro.2013.02.103. Epub 2013 Feb 28.


Purpose: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck.

Materials and methods: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension.

Results: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+).

Conclusions: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation.

Keywords: 4-AP; 4-aminopyridine; AM; ATP; ATP dependent K(+); CGRP; COX; CSE; CSPA; Ca(2+) activated K(+); Emax; K(ATP); K(Ca); K(V); KPSS; L-NOARG; MLCP; N(G)-nitro-L-arginine; NO; PACAP; PKA; PSS; TRPA(1); TRPV(1); VOC; VPAC; [Ca(2+)](i); acetoxymethyl ester; adenosine 5′-triphosphate; calcitonin gene-related peptide; capsaicin sensitive primary afferent; cyclooxygenase; cystathionine γ-lyase; hydrogen sulfide; intracellular Ca(2+); maximum response; muscle, smooth; myosin light chain phosphatase; nitric oxide; physiological saline solution; pituitary adenylyl cyclase activating polypeptide; potassium channels; potassium rich PSS; protein kinase A; synaptic transmission; transient receptor potential A1; transient receptor potential vanilloid 1; urinary bladder; vasoactive intestinal peptide receptor; voltage gated Ca(2+); voltage gated K(+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Acrylamides / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcium Signaling / drug effects*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / pharmacology
  • Electric Stimulation
  • Glyburide / pharmacology
  • Guanylate Cyclase / pharmacology
  • Hydrogen Sulfide / pharmacology*
  • Indomethacin / pharmacology
  • KATP Channels / metabolism*
  • Morpholines / pharmacology
  • Muscle, Smooth / drug effects*
  • Organothiophosphorus Compounds / pharmacology
  • Phenylephrine / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Purines / pharmacology
  • Pyrazoles / pharmacology
  • Sensory Receptor Cells / metabolism*
  • Swine
  • Synaptic Transmission / drug effects*
  • Urinary Bladder / innervation*
  • Urinary Bladder / metabolism*


  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acetanilides
  • Acrylamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • GYY 4137
  • KATP Channels
  • Morpholines
  • Organothiophosphorus Compounds
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Purines
  • Pyrazoles
  • SC 560
  • Phenylephrine
  • Cyclic AMP-Dependent Protein Kinases
  • Guanylate Cyclase
  • Calcitonin Gene-Related Peptide
  • capsazepine
  • Capsaicin
  • Glyburide
  • Indomethacin
  • Hydrogen Sulfide