title: Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect of hydrogen sulfide against stress-induced gastric lesions.
abstract: Hydrogen sulfide (H2S) plays an important role in human physiology, exerting vasodilatory, neuromodulatory and anti-inflammatory effects. H2S has been implicated in the mechanism of gastrointestinal integrity but whether this gaseous mediator can affect hemorrhagic lesions induced by stress has been little elucidated. We studied the effect of the H2S precursor L-cysteine, H2S-donor NaHS, the H2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine (PAG) and the gastric H2S production by CSE/CBS/3-MST activity in water immersion and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism of gastroprotection induced by H2S was examined in capsaicin-denervated rats and those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR-1). Rats were pretreated with vehicle, NaHS, the donor of H2S and or L-cysteine, the H2S precursor, with or without the concurrent treatment with 1) nonselective (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib) inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L-cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and significantly increased GBF. These effects were significantly reduced by pretreatment with PAG and capsaicin denervation. NaHS increased gastric H2S production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2 activity significantly diminished NaHS- and L-cysteine-induced protection and hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein contents were reversed by PAG and capsaicin denervation. We conclude that H2S exerts gastroprotection against WRS-induced gastric lesions by the mechanism involving enhancement in gastric microcirculation mediated by endogenous PGs, sensory afferent nerves releasing CGRP and the activation of VR-1 receptors.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Magierowski
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jasnos
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Drozdowicz
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Surmiak
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Strzalka
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptak-Belowska
authors.affiliation: Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada.
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
mesh_terms: D000480:Alkynes / Q000276:immunology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology; D051545:Cyclooxygenase 1 / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000276:immunology; D003545:Cysteine / Q000276:immunology; D005753:Gastric Mucosa / Q000098:blood supply / Q000276:immunology / Q000294:innervation / Q000503:physiopathology; D005998:Glycine / Q000031:analogs & derivatives / Q000276:immunology; D006862:Hydrogen Sulfide / Q000276:immunology*; D008297:Male; D011453:Prostaglandins / Q000276:immunology*; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000276:immunology* / Q000473:pathology; D013270:Stomach / Q000098:blood supply / Q000276:immunology / Q000294:innervation / Q000503:physiopathology*; D013312:Stress, Physiological
chemical_list: D000480:Alkynes; D011453:Prostaglandins; C009055:propargylglycine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015740:Calcitonin Gene-Related Peptide; D003545:Cysteine; D005998:Glycine; D006862:Hydrogen Sulfide