Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle.
We have investigated the mechanism through which hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat isolated urinary bladder. Sodium hydrogen sulfide (NaHS), a donor of H2S, produced concentration-dependent contractile responses (pEC50=3.5+/-0.1) that were unaffected by the transient receptor potential vanilloid receptor 1 (TRPV1) antagonist capsazepine (30 microM) and SB 366791 (10 microM) and by the N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CTX; 100 nM). In contrast, the unselective transient receptor potential (TRP) cation channels blocker ruthenium red (30 microM) almost abolished NaHS-induced contractions. Ruthenium red (30 microM) greatly reduced capsaicin-induced contractions, whereas it did not attenuate the contractile response to neurokinin A. The putative TRPV1 receptor antagonist iodo-resiniferatoxin, from 100 nM upward, produced agonist responses per se, and could not be tested against NaHS. We conclude that H2S either acts at TRPV1 receptorial sites unblocked by capsazepine or SB 366791, or stimulates a still unidentified transient receptor potential-like channel co-expressed with TRPV1 on sensory neurons.
Patacchini
Riccardo
R
Department of Pharmacology, Menarini Ricerche SpA, via Rismondo 12/A, 50131, Florence, Italy. r.patacchini@chiesigroup.com
Santicioli
Paolo
P
Giuliani
Sandro
S
Maggi
Carlo Alberto
CA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D004224:Diterpenes; D013440:Sulfides; C468130:iodoresiniferatoxin; D012430:Ruthenium Red; D015288:Neurokinin A; D020866:omega-Conotoxin GVIA; C025451:sodium bisulfide; D002211:Capsaicin; D006862:Hydrogen Sulfide