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SHR Neuro Cancer Cardio Lipid Metab Microb

Schicho, R; Krueger, D; Zeller, F; Von Weyhern, CW; Frieling, T; Kimura, H; Ishii, I; De Giorgio, R; Campi, B; Schemann, M.
Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon.
Gastroenterology. 2006; 131(5): 1542-1552. Doi: 10.1053/j.gastro.2006.08.035
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Leading authors Med Uni Graz: Schicho Rudolf
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Abstract:: BACKGROUND & AIMS: Hydrogen sulfide (H(2)S) has been suggested as a novel gasomediator. We explored its unknown neuromodulatory role in human and guinea-pig colon. METHODS: We used immunohistochemistry to detect H(2)S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in enteric neurons, Ussing chambers to measure mucosal ion secretion, and neuroimaging with voltage- and Ca(++)-sensitive dyes to record H(2)S effects on guinea-pig and human enteric neurons. RESULTS: More than 90% of guinea-pig and human submucous and myenteric neurons were colabeled for CSE and CBS. Myenteric interstitial cells of Cajal were CSE-immunoreactive. The exogenous H(2)S donor NaHS (0.2-2.5 mmol/L) concentration-dependently increased chloride secretion in human and guinea-pig submucosa/mucosa preparations, but not in the colonic epithelial cell line T84. The secretory response was reduced significantly by tetrodotoxin (0.5 micromol/L), capsaicin desensitization (10 micromol/L), and the transient receptor potentials vanilloid receptor 1 antagonist capsazepine (10 micromol/L). The endogenous H(2)S donor L-cysteine also induced secretion that was diminished significantly by capsaicin desensitization, the CBS inhibitor amino-oxyacetic acid, and the CSE inhibitor propargylglycine. NaHS increased spike discharge in 23% of guinea-pig and 36% of human submucous neurons, but had no effect on Ca(++) mobilization in cultured guinea-pig enteric neurons. This excitatory response was reduced significantly by capsaicin desensitization and capsazepine, but not by glibenclamide (10 micromol/L). CONCLUSIONS: The presence of H(2)S-producing enzymes in human and guinea-pig enteric neurons, the excitatory action on enteric neurons, and the prosecretory effects of NaHS suggest H(2)S as a novel gut-signaling molecule. Its action mainly involves transient receptor potentials vanilloid receptor 1 receptors on extrinsic afferent terminals, which in turn activate enteric neurons.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Aged, 80 and over -; Animals -; Calcium - metabolism; Cell Line -; Colon - drug effects Colon - secretion; Cystathionine beta-Synthase - analysis; Cystathionine gamma-Lyase - analysis; Cysteine - pharmacology; Dose-Response Relationship, Drug -; Female -; Guinea Pigs -; Humans -; Hydrogen Sulfide - pharmacology; Intestinal Mucosa - drug effects Intestinal Mucosa - innervation Intestinal Mucosa - secretion; Male -; Middle Aged -; Potassium Channels - drug effects; TRPV Cation Channels - drug effects