title: H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.
abstract: Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion.
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan; General Incorporated Association, Kyoto Research Center for Gastrointestinal Diseases, Karasuma-Oike, 671, Kyoto 604-8106, Japan. Electronic address: takeuchi@mb.kyoto-phu.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ise
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Aihara
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D013440:Sulfides
chemical_list: D001639:Bicarbonates; D011453:Prostaglandins; D013440:Sulfides; D009569:Nitric Oxide; C025451:sodium bisulfide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D006862:Hydrogen Sulfide
keywords: Capsaicin-sensitive sensory neurons; Gastric HCO(3)(−) secretion; H(2)S; Nitric oxide; Prostaglandins