RT Journal Article SR Electronic T1 Evidence That Hydrogen Sulfide Exerts Antinociceptive Effects in the Gastrointestinal Tract by Activating KATP Channels JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 325 OP 335 DO 10.1124/jpet.105.091595 VO 316 IS 1 A1 Eleonora Distrutti A1 Luca Sediari A1 Andrea Mencarelli A1 Barbara Renga A1 Stefano Orlandi A1 Elisabetta Antonelli A1 Fiorenza Roviezzo A1 Antonio Morelli A1 Giuseppe Cirino A1 John L. Wallace A1 Stefano Fiorucci YR 2006 UL http://jpet.aspetjournals.org/content/316/1/325.abstract AB Hydrogen sulfide (H2S) functions as a neuromodulator, but whether it modulates visceral perception and pain is unknown. Cystathionineβ -synthase (CBS) and cystathionine-γ-lyase (CSE) mediate enzymatic generation of H2S in mammalian cells. Here we have investigated the role of H2S in modulating nociception to colorectal distension, a model that mimics some features of the irritable bowel syndrome. Four graded (0.4–1.6 ml of water) colorectal distensions (CRDs) were produced in conscious rats (healthy and postcolitic), and rectal nociception was assessed by measuring the behavioral response during CRD. Healthy rats were administered with sodium hydrogen sulfide (NaHS) (as a source of H2S), l-cysteine, or vehicle. In a second model, we investigated nociception to CRD in rats recovering from a chemically induced acute colitis. We found that CBS and CSE are expressed in the colon and spinal cord. Treating rats with NaHS resulted in a dose-dependent attenuation of CRD-induced nociception with the maximal effect at 60 μmol/kg (p< 0.05). Administration of l-cysteine, a CSE/CBS substrate, reduced rectal sensitivity to CRD (p < 0.05). NaHS-induced antinociception was reversed by glibenclamide, a ATP-sensitive K+ (KATP) channel inhibitor, and Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nitric-oxide (NO) synthase inhibitor. The antinociceptive effect of NaHS was maintained during the resolution of colon inflammation induced by intrarectal administration of a chemical irritant. In summary, these data show that H2S inhibits nociception induced by CRD in both healthy and postcolitic rats. This effect is mediated by KATP channels and NO. H2S-releasing drugs might be beneficial in treating painful intestinal disorders. The American Society for Pharmacology and Experimental Therapeutics