Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus

Dhaese, Ingeborg; Lefebvre, Romain

doi:10.1016/j.ejphar.2009.01.011

Cited by 62 publications

(73 citation statements)

References 40 publications

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“…Vascular tone is dependent on the relative activities of MLC kinase and MLCP, where activation of MLC kinase or inhibition of MLCP can increase phosphorylation of MLC and thereby initiate vascular smooth muscle contraction (Somlyo and Somlyo, 2003). Inhibition of MLCP, but not Rho-kinase, reduced the H 2 S-induced relaxation of mouse gastrointestinal smooth muscle (Dhaese and Lefebvre, 2009); in the pig bladder, H 2 S lowered tension without changing the calcium concentration (Fernandes et al, 2013). In our study, H 2 S initially evoked vasodilation while the intracellular calcium levels increased or were maintained at the same level.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide–Induced Relaxation of Rat Mesenteric Small Arteries

Hedegaard

Gouliaev

Winther

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

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Endogenous hydrogen sulfide (H 2 S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calciumindependent mechanisms are involved in H 2 S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H 2 S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na 2 S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H 2 S], GYY4137 caused more relaxation in relation to released free H 2 S than NaHS and Na 2 S in rat mesenteric small arteries. Simultaneous measurements of [H 2 S] and tension showed that 15 mM of free H 2 S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated K V 7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H 2 S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation.

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Section: Discussionmentioning

confidence: 99%

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide–Induced Relaxation of Rat Mesenteric Small Arteries

Hedegaard

Gouliaev

Winther

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

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“…Salmonid tissues, however, appear to be more sensitive to H 2 S. Although few studies have provided detailed concentrationresponse characterization of the effects of H 2 S in the mammalian GI tract, most studies suggest that the threshold for a response is 10mmoll -1 or above and EC 50 values (either provided by the authors or estimated from their data) are usually well above 300mmoll -1 . In the mouse gastric fundus pre-contracted with prostaglandin F2 (PGF 2 ), relaxation was first observed at 10mmoll -1 and EC 50 values ranged from 350 to 429mmoll -1 (Dhaese and Lefebvre, 2009). In the guinea-pig stomach, 10mmoll -1 H 2 S significantly enhanced resting tension and slightly reduced the contractile amplitude, whereas 300mmoll -1 H 2 S suppressed spontaneous contractions (Zhao et al, 2009).…”

Section: Comparison Of H 2 S Effects In Mammals and Troutmentioning

confidence: 99%

“…H 2 S directly relaxes GI smooth muscle in the mouse stomach and colon (Dhaese and Lefebvre, 2009;Dhaese et al, 2010) and rat ileum (Nagao et al, 2010). In the guinea-pig stomach, 'low doses' of H 2 S (0.1-0.3mmoll -1 ) enhance resting tension and slightly reduce contractile amplitude, whereas at higher concentrations H 2 S suppresses the amplitude of spontaneous contractions (Zhao et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of H 2 S-mediated relaxation is poorly understood and most common mediators of muscle relaxation have in fact been ruled out. In the mouse, H 2 S-induced relaxations are independent of potassium (K + ) channels, NO, cAMP and cGMP pathways, and nerve inhibition, and do not involve membrane H 2 S and GI motility in salmonids ATPase, calcium (Ca 2+ ) channels, internal calcium stores or Rhokinase; H 2 S may, or may not, act via activation of myosin light chain phosphatase (Dhaese and Lefebvre, 2009;Dhaese et al, 2010). In the rat ileum, H 2 S-mediated relaxations are independent of intrinsic, enteric and visceral afferent nerves, NO and both ATP-(K ATP ) and calcium-sensitive (K Ca ) potassium channels (Nagao et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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“…The exact mechanism of the relaxant effect was unclear because it was not associated with the activation of potassium channels including KATP channels, Ca 2+ -activated K + channel, voltage dependent K + channel and inward rectifier K + channel, the release of NO, and not influenced by TTX, a nerve blockers. However, the inhibitory effect of NaHS on PGF2α-induced contraction was suppressed by calyculin-A, an inhibitor of myosin light chain phosphatase (MLCP), the result suggests H2S may be directly participated in MLCP phosphorilation [42] . Generally speaking, the effect of H2S on the gastric motility seems to be adapted to the function of the stomach.…”

Section: In the Stomachmentioning

confidence: 87%

Synthesis of H2S in the Gastrointestinal Tract

Huang

2015

Journal of Gastroenterology and Hepatology Research

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Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus

Cited by 62 publications

References 40 publications

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide–Induced Relaxation of Rat Mesenteric Small Arteries

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide–Induced Relaxation of Rat Mesenteric Small Arteries

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

Synthesis of H2S in the Gastrointestinal Tract

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