Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility

作者: V Gil , D Gallego , M Jiménez

DOI: 10.1111/J.1476-5381.2011.01431.X

关键词: BiochemistryPharmacologyCystathionine gamma-lyaseNitric oxideChemistryTetrodotoxinCystathionine beta synthaseMotilityEndogenyDepolarizationHyperpolarization (biology)

摘要: BACKGROUND AND PURPOSE The role of hydrogen sulphide (H2S) as a putative endogenous signalling molecule in the gastrointestinal tract has not yet been established. We investigated effect D,L-propargylglycine (PAG), an inhibitor cystathionine γ-lyase (CSE), amino-oxyacetic acid (AOAA) and hydroxylamine (HA), inhibitors β-synthase (CBS) on rat colonic motility. EXPERIMENTAL APPROACH Immunohistochemistry, H2S production, microelectrode organ bath recordings were performed samples without mucosa submucosa to investigate motility. KEY RESULTS CSE CBS immunolocalized colon. was endogenously produced (15.6 ± 0.7 nmol·min−1·g−1 tissue) its production strongly inhibited by PAG (2 mM) AOAA (2 mM). caused smooth muscle depolarization increased spontaneous motility. still recorded after incubation with tetrodotoxin (TTX, 1 µM) or Nω-nitro-L-arginine (L-NNA, 1 mM). transient (10 min) increase In contrast, HA (10 µM) ‘nitric oxide-like effect’, hyperpolarization relaxation, which antagonized 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 10 µM). Neither nor induced inhibitory junction potentials modified PAG. CONCLUSIONS IMPLICATIONS demonstrated that is effectively blocked production. Our data suggest enzymatic regulates motility therefore might be third gaseous tract. However, possible non-specific effects should considered.

参考文章(46)
John T. Barron, Liping Gu, Jospeh E. Parrillo, Relation of NADH/NAD to contraction in vascular smooth muscle. Molecular and Cellular Biochemistry. ,vol. 194, pp. 283- 290 ,(1999) , 10.1023/A:1006928516648
B Hennig, M Diener, Actions of hydrogen sulphide on ion transport across rat distal colon. British Journal of Pharmacology. ,vol. 158, pp. 1263- 1275 ,(2009) , 10.1111/J.1476-5381.2009.00385.X
D. Krueger, M. Foerster, K. Mueller, F. Zeller, J. Slotta-huspenina, J. Donovan, D. Grundy, M. Schemann, Signaling mechanisms involved in the intestinal pro‐secretory actions of hydrogen sulfide Neurogastroenterology and Motility. ,vol. 22, pp. 1224- ,(2010) , 10.1111/J.1365-2982.2010.01571.X
Laura Grasa, Víctor Gil, Diana Gallego, Maria Teresa Martín, Marcel Jiménez, P2Y1 receptors mediate inhibitory neuromuscular transmission in the rat colon British Journal of Pharmacology. ,vol. 158, pp. 1641- 1652 ,(2009) , 10.1111/J.1476-5381.2009.00454.X
M H Stipanuk, P W Beck, Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat Biochemical Journal. ,vol. 206, pp. 267- 277 ,(1982) , 10.1042/BJ2060267
S Fiorucci, S Orlandi, A Mencarelli, G Caliendo, V Santagada, E Distrutti, L Santucci, G Cirino, J L Wallace, Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis. British Journal of Pharmacology. ,vol. 150, pp. 996- 1002 ,(2007) , 10.1038/SJ.BJP.0707193
E Pouokam, M Diener, Mechanisms of actions of hydrogen sulphide on rat distal colonic epithelium. British Journal of Pharmacology. ,vol. 162, pp. 392- 404 ,(2011) , 10.1111/J.1476-5381.2010.01026.X
Kyu Joo Park, Salah A Baker, Sang Yun Cho, Kenton M Sanders, Sang Don Koh, Sulfur‐containing amino acids block stretch‐dependent K+ channels and nitrergic responses in the murine colon British Journal of Pharmacology. ,vol. 144, pp. 1126- 1137 ,(2005) , 10.1038/SJ.BJP.0706154
Marina Casimir, Blanca Rubi, Francesca Frigerio, Gaelle Chaffard, Pierre Maechler, Silencing of the mitochondrial NADH shuttle component aspartate-glutamate carrier AGC1/Aralar1 in INS-1E cells and rat islets Biochemical Journal. ,vol. 424, pp. 459- 466 ,(2009) , 10.1042/BJ20090729
Eric Southam, John Garthwaite, Comparative effects of some nitric oxide donors on cyclic GMP levels in rat cerebellar slices. Neuroscience Letters. ,vol. 130, pp. 107- 111 ,(1991) , 10.1016/0304-3940(91)90239-P