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Muscarinic and hydrogen sulfide

Oladayo Folasire, Kylie A Mills, Donna J Sellers, Russ Chess-Williams
BACKGROUND/AIMS: The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. METHODS: Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems...
January 31, 2016: Journal of Neurogastroenterology and Motility
Amira Moustafa, Yoshiaki Habara
In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist upregulated endothelial NO synthase in parotid tissue. NO and H2S donors increased the intracellular Ca(2+) concentration ([Ca(2+)]i)...
October 1, 2015: American Journal of Physiology. Cell Physiology
Vítor S Fernandes, Wenkuan Xin, Georgi V Petkov
Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca(2+) imaging, and patch-clamp electrophysiology...
July 15, 2015: American Journal of Physiology. Cell Physiology
Guanghua Tang, Guangdong Yang, Bo Jiang, Youngjun Ju, Lingyun Wu, Rui Wang
AIMS: Endothelium-dependent vasorelaxation is mediated by endothelium-derived relaxing factor and endothelium-derived hyperpolarizing factor (EDHF). However, the molecular entity of EDHF remains unclear. The present study examined whether hydrogen sulfide (H₂S) acts as EDHF and how H₂S mediates EDHF pathways from endothelial origination to downstream target of smooth muscle cells (SMCs). RESULTS: We found that knocking-out the expression of cystathionine γ-lyase (CSE) in mice (CSE-knockout [KO]) elevated resting-membrane-potential of SMCs and eliminated methacholine-induced endothelium-dependent relaxation of mesenteric arteries, but not that of aorta...
November 10, 2013: Antioxidants & Redox Signaling
S Rashid, J K Heer, M J Garle, S P H Alexander, R E Roberts
BACKGROUND AND PURPOSE: Hydrogen sulphide (H2S) is an endogenous gasotransmitter. Although it has been shown to elicit responses in vascular and other smooth muscle preparations, a role for endogenously produced H2S in mediating airway tone has yet to be demonstrated. Therefore, the aim of this study was to determine whether H2S is produced within the airways and to determine the functional effect on airway tone. EXPERIMENTAL APPROACH: Small peripheral airways (<5 mm in diameter) from porcine lungs were set up in isolated tissue baths, pre-contracted with the muscarinic agonist carbachol, and then exposed to either the H2S donor sodium hydrosulphide (NaHS), or the precursor L-cysteine...
April 2013: British Journal of Pharmacology
Munenori Nagao, Judith A Duenes, Michael G Sarr
AIM: Our aim was to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H(2)S) on contractile activity in circular muscle of rat jejunum. METHODS: Jejunal circular muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a H(2)S donor, were evaluated on spontaneous contractile activity and after pre-contraction with bethanechol. L-cysteine was evaluated as an endogenous H(2)S donor. We evaluated extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, K(ATP)+ and K(Ca)+ channels, and myosin light chain phosphatase on action of H(2)S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L-N(G)-nitro arginine (L-NNA), glibenclamide, apamin, and calyculin A, respectively, and electrical field stimulation (EFS)...
February 2012: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
Sunny E Ohia, Catherine A Opere, Emmanuel M Monjok, Ghislaine Kouamou, Angela M Leday, Ya Fatou Njie-Mbye
PURPOSE: To investigate the direct pharmacological actions of L-cysteine, a substrate for the production of H(2)S, on isolated porcine irides in the presence of tone induced by muscarinic receptor stimulation. Furthermore, we examined the underlying mechanism of action of L-cysteine in this smooth muscle. METHODS: Isolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution at 37 degrees C. Longitudinal isometric tension was recorded via a grass FT03 Force-Displacement Transducer and analyzed using the PolyView computer software...
May 2010: Current Eye Research
Rui Wang
The first endothelium-derived relaxing factor (EDRF) ever identified is a gasotransmitter, nitric oxide (NO). Recent studies have provided several lines of evidence to support the premise that hydrogen sulfide (H(2)S), another gasotransmitter, is a new EDRF. H(2)S production is catalyzed in mammalian cells by cystathionine beta-synthase (CBS) and/or cystathionine gamma-lyase (CSE). The expression of CSE proteins and the activity of CBS have been observed in vascular endothelial cells. A measurable amount of H(2)S is produced from endothelium upon muscarinic cholinergic stimulation...
October 2009: Kidney International
Emmanuel M Monjok, Kaustubh H Kulkarni, Ghislaine Kouamou, Marshalyn McKoy, Catherine A Opere, Odelia N Bongmba, Ya Fatou Njie, Sunny E Ohia
We investigated the pharmacological actions of hydrogen sulfide (H(2)S) using sodium hydrosulfide (NaHS) and sodium sulfide (Na(2)S) as donors on isolated porcine irides in the presence of tone induced by muscarinic receptor stimulation. Furthermore, we also investigated the mechanism of action of H(2)S in this smooth muscle. Isolated porcine iris muscle strips were set up in organ baths and prepared for measurement of longitudinal isometric tension. The relaxant action of NaHS or Na(2)S on carbachol-induced tone was studied in the absence and presence of a K(+)-channel inhibitor and inhibitors/activators of enzymes of the biosynthetic pathways for H(2)S, prostanoid and nitric oxide production...
December 2008: Experimental Eye Research
Ryan A Dombkowski, Michael J Russell, Kenneth R Olson
Hydrogen sulfide (H(2)S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H(2)S from NaHS and examined the effects on isolated efferent branchial arteries from steelhead (stEBA) or rainbow (rtEBA) trout. H(2)S concentration was measured colorimetrically (CM) and with ion-selective electrodes (ISE) in rainbow trout plasma. NaHS produced a triphasic response consisting of a relaxation (phase 1), constriction (phase 2), and relaxation (phase 3) in both unstimulated vessels and in stEBA precontracted with carbachol (Carb)...
April 2004: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
H Pedersen, H Bräuner-Osborne, R G Ball, K Frydenvang, E Meier, K P Bøgesø, P Krogsgaard-Larsen
A series of O- and ring-alkylated derivatives of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol was synthesized via treatment of appropriately substituted 4-benzylamino-1,2,5,6-tetrahydropyridine-3-carboxamides with hydrogen sulfide and subsequent ring closure by oxidation with bromine. The muscarinic receptor affinity as well as estimated relative efficacy and subtype selectivity of this series of bicyclic arecoline bioisosteres were determined using rat brain membranes and a number of tritiated muscarinic receptor ligands...
May 1999: Bioorganic & Medicinal Chemistry
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