Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder

In the rat isolated urinary bladder, NaHS (30 muM-3mM) and capsaicin (10 nM-3muM) produced concentration-dependent contractile responses (pEC(50) = 3.5 +/- 0.02 and 7.1 +/- 0.02, respectively) undergoing dramatic tachyphylaxis. In preparations in which sensory nerves were rendered desensitized (defunctionalized) by high-capsaicin (10 muM for 15 min) pretreatment, neither capsaicin itself nor NaHS produced any motor effect. NaHS-induced contractile effects were totally prevented by the simultaneous incubation with tachykinin NK1 (GR 82334; 10 muM) and NK2 (nepadutant; 0.3 muM) receptor-selective antagonists. Tetrodotoxin (1 muM) only partially reduced the response to NaHS. These results provide pharmacological evidence that H2S stimulates capsaicin-sensitive primary afferent nerve terminals, from which tachykinins are released to produce the observed contraction by activating NK1 and NK2 receptors. While the molecular site of action of H2S remains to be investigated, our discovery may have important physiological significance since H2S concentrations capable of stimulating sensory nerves overlap those occurring in mammalian tissues under normal conditions.