Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder.
In the rat isolated urinary bladder, NaHS (30 microm-3 mm) and capsaicin (10 nm-3 microm) 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 microm 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 microm) and NK(2) (nepadutant; 0.3 microm) receptor-selective antagonists. Tetrodotoxin (1 microm) 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.
Patacchini
Riccardo
R
Department of Pharmacology, Menarini Ricerche, Via Rismondo 12/A, Florence 50131, Italy. chimfarm@menarini-ricerche.it
Santicioli
Paolo
P
Giuliani
Sandro
S
Maggi
Carlo Alberto
CA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D002211:Capsaicin; D006862:Hydrogen Sulfide