Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract

Martin, Gary R.; McKnight, G. Webb; Dicay, Michael; Coffin, Carla S.; Ferraz, José G.; Wallace, John L.

doi:10.1016/j.dld.2009.05.016

Cited by 107 publications

(84 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…mRNA for both enzymes was found to be present (Fig. 1A), consistent with previous reports (24,29). To determine cellular expression of CSE and CBS, we carried out immunohistochemistry on human jejunum fresh-frozen sections.…”

Section: Resultssupporting

confidence: 70%

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Strege

Bernard

Kraichely

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

gen sulfide (H 2S) is produced endogenously by L-cysteine metabolism. H 2S modulates several ion channels with an unclear mechanism of action. A possible mechanism is through reduction-oxidation reactions attributable to the redox potential of the sulfur moiety. The aims of this study were to determine the effects of the H 2S donor NaHS on Na V1.5, a voltage-dependent sodium channel expressed in the gastrointestinal tract in human jejunum smooth muscle cells and interstitial cells of Cajal, and to elucidate whether H 2S acts on NaV1.5 by redox reactions. Whole cell Na ϩ currents were recorded in freshly dissociated human jejunum circular myocytes and Na V1.5-transfected human embryonic kidney-293 cells. RT-PCR amplified mRNA for H 2S enzymes cystathionine ␤-synthase and cystathionine ␥-lyase from the human jejunum. NaHS increased native Na ϩ peak currents and shifted the half-point (V 1/2) of steady-state activation and inactivation by ϩ21 Ϯ 2 mV and ϩ15 Ϯ 3 mV, respectively. Similar effects were seen on the heterologously expressed Na V1.5 ␣ subunit with EC50s in the 10 Ϫ4 to 10 Ϫ3 M range. The reducing agent dithiothreitol (DTT) mimicked in part the effects of NaHS by increasing peak current and positively shifting steady-state activation. DTT together with NaHS had an additive effect on steady-state activation but not on peak current, suggesting that the latter may be altered via reduction. Pretreatment with the Hg 2ϩ -conjugated oxidizer thimerosal or the alkylating agent N-ethylmaleimide inhibited or decreased NaHS induction of NaV1.5 peak current. These studies show that H2S activates the gastrointestinal Na ϩ channel, and the mechanism of action of H2S is partially redox independent. patch clamp; intestine; smooth muscle; dithiothreitol; thimerosal HYDROGEN SULFIDE (H 2 S) IS A GAS produced endogenously through L-cysteine metabolism predominantly by two enzymes, cystathione ␥-lyase (CSE) and cystathione ␤-synthase (CBS) (reviewed in Refs. 4,14,19). H 2 S is detected in mammalian tissues and in circulation. Moreover, H 2 S and/or HS Ϫ have been shown to be an active molecule, with clear pharmacological effects on smooth muscle tissues, including relaxation of vascular, corpus cavernosum, uterine, and gastrointestinal smooth muscle.Ion channels regulate contractility of gastrointestinal smooth muscle. H 2 S is known to target various ion channels. Evidence for this involvement of channel activity is strongest for the K ATP channel with some evidence for modulation of BK, Cl Ϫ , and L-type and T-type Ca 2ϩ channels (15,19,42). In human intestinal smooth muscle cells, channels that allow entry of ions into the cell include Na V 1.5 [Na ϩ current: (10, 27, 38, 48), Ca V 1.2 L-type Ca 2ϩ current: (6, 7, 22, 47), Ca V 3.2 T-type Ca 2ϩ current: (8, 47)], and nonselective cation channels (16). The mechanism by which H 2 S modulates ion-channel activity is still largely unknown, and, although the chemistry of H 2 S favors redox modification of proteins, there has been little study of this effect. H 2 S and alterna...

show abstract

Section: Resultssupporting

confidence: 70%

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Strege

Bernard

Kraichely

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…H 2 S is of particular interest in the gastrointestinal (GI) tract as it is both produced by GI tissues and generated in large quantities by bacterial flora in the lumen of the gut Hosoki et al, 1997;Linden et al, 2008;Martin et al, 2010;Teague et al, 2002;Wallace, 2010). Both pathological and physiological attributes have been ascribed to H 2 S in the GI tract (Wallace, 2010).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

Dombkowski

Naylor

Shoemaker

et al. 2011

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYHydrogen sulfide (H 2 S) has been shown to affect gastrointestinal (GI) motility and signaling in mammals and O 2 -dependent H 2 S metabolism has been proposed to serve as an O 2 ʻsensorʼ that couples hypoxic stimuli to effector responses in a variety of other O 2 -sensing tissues. The low P O2 values and high H 2 S concentrations routinely encountered in the GI tract suggest that H 2 S might also be involved in hypoxic responses in these tissues. In the present study we examined the effect of H 2 S on stomach, esophagus, gallbladder and intestinal motility in the rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch) and we evaluated the potential for H 2 S in oxygen sensing by examining GI responses to hypoxia in the presence of known inhibitors of H 2 S biosynthesis and by adding the sulfide donor cysteine (Cys). We also measured H 2 S production by intestinal tissue in real time and in the presence and absence of oxygen. In tissues exhibiting spontaneous contractions, H 2 S inhibited contraction magnitude (area under the curve and amplitude) and frequency, and in all tissues it reduced baseline tension in a concentration-dependent relationship. Longitudinal intestinal smooth muscle was significantly more sensitive to H 2 S than other tissues, exhibiting significant inhibitory responses at 1-10mmoll -1 H 2 S. The effects of hypoxia were essentially identical to those of H 2 S in longitudinal and circular intestinal smooth muscle; of special note was a unique transient stimulatory effect upon application of both hypoxia and H 2 S. Inhibitors of enzymes implicated in H 2 S biosynthesis (cystathionine -synthase and cystathionine -lyase) partially inhibited the effects of hypoxia whereas the hypoxic effects were augmented by the sulfide donor Cys. Furthermore, tissue production of H 2 S was inversely related to O 2 ; addition of Cys to intestinal tissue homogenate stimulated H 2 S production when the tissue was gassed with 100% nitrogen (~0% O 2 ), whereas addition of oxygen (~10% O 2 ) reversed this to net H 2 S consumption. This study shows that the inhibitory effects of H 2 S on the GI tract of a non-mammalian vertebrate are identical to those reported in mammals and they provide further evidence that H 2 S is a key mediator of the hypoxic response in a variety of O 2 -sensitive tissues.

show abstract

“…Western blotting results also demonstrated that both CBS and CSE were expressed in the rat and mouse stomach, and H2S synthesis in the rat stomach was about 75 nmol/g/h [25] . CBS and CSE were also identified in the small intestine [25][26][27][28][29][30] . In the rat duodenum and jejunum, both enzymes were expressed in the neurons of myenteric plexus, but not the smooth muscle cells or the interstitial cells of Cajal (ICCs) [27,29] .…”

Section: Ynthesis Of H2s In the Gastrointestinal Tractmentioning

confidence: 82%

“…The most important problem is that the present used inhibitors of CBS and CSE are considered nonspecific, especially AOAA which was proved to inhibit other pyridoxal phoophate-dependent enzymes [52,53] . Although it has been the exclusive inhibitor of CBS so far and also proved to reduce the generation of H2S [25,34] , the possible side effects of AOAA make it suspect to speculate the function of endogenous H2S. Using the animals targeted deleted CBS and CSE may be an effective method to study the function of endogenous H2S in the gastrointestinal tract.…”

Section: Problems In Studiesmentioning

confidence: 99%

Synthesis of H2S in the Gastrointestinal Tract

Huang

2015

Journal of Gastroenterology and Hepatology Research

View full text Add to dashboard Cite

Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract

Cited by 107 publications

References 39 publications

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

Synthesis of H2S in the Gastrointestinal Tract

Contact Info

Product

Resources

About

Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract

Cited by 107 publications

References 39 publications

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na+ channel, Nav1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na+ channel, Nav1.5

Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

Synthesis of H2S in the Gastrointestinal Tract

Contact Info

Product

Resources

About

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5