Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon.
OBJECTIVE
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.
Schicho
Rudolf
R
Department of Human Biology, Technical University Munich, Munich, Germany.
Krueger
Dagmar
D
Zeller
Florian
F
Von Weyhern
Claus Werner Hann
CW
Frieling
Thomas
T
Kimura
Hideo
H
Ishii
Isao
I
De Giorgio
Roberto
R
Campi
Barbara
B
Schemann
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000032:analysis; D003542:Cystathionine gamma-Lyase / Q000032:analysis; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000187:drug effects; D050916:TRPV Cation Channels / Q000187:drug effects
D015221:Potassium Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D002118:Calcium; D006862:Hydrogen Sulfide