Hydrogen sulfide (H 2 S) stimulates capsaicin‐sensitive primary afferent neurons in the rat urinary bladder

In the rat isolated urinary bladder, NaHS (30 μ M –3 m M ) and capsaicin (10 n M –3 μ M ) 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 μ M 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 NK 1 (GR 82334; 10 μ M ) and NK 2 (nepadutant; 0.3 μ M ) receptor‐selective antagonists. Tetrodotoxin (1 μ M ) only partially reduced the response to NaHS. These results provide pharmacological evidence that H 2 S stimulates capsaicin‐sensitive primary afferent nerve terminals, from which tachykinins are released to produce the observed contraction by activating NK 1 and NK 2 receptors. While the molecular site of action of H 2 S remains to be investigated, our discovery may have important physiological significance since H 2 S concentrations capable of stimulating sensory nerves overlap those occurring in mammalian tissues under normal conditions.British Journal of Pharmacology (2004) 142 , 31–34. doi: 10.1038/sj.bjp.0705764