TY - JOUR
T1 - Hydrogen sulfide modulates contractile function in rat jejunum
AU - Kasparek, Michael S.
AU - Linden, David R.
AU - Farrugia, Gianrico
AU - Sarr, Michael G.
N1 - Funding Information:
The authors thank Judith A. Duenes for the technical support and Deborah I. Frank for the assistance in the preparation of this manuscript. This research was supported by grant DK R01 39337-18 from the National Institutes of Health, United States Public Health Services (MGS) and grant KA 2329/1-1 from the Deutsche Forschungsgemeinschaft , Germany (MSK).
PY - 2012/6/15
Y1 - 2012/6/15
N2 - Background: Effects of hydrogen sulfide (H 2S), a third gasotransmitter of the gut, are not well understood. The aim of this study was to determine effects/mechanisms of H 2S action on contractile function in rat jejunal muscle. Methods: Transmural strips of longitudinal muscle were evaluated. Response to sodium hydrosulfide (NaHS, H 2S donor; 10 -5-10 -3M) was studied on spontaneous contractile activity and after precontraction (bethanechol, 3 × 10 -6M). Atropine, propranolol, phentolamine, tetrodotoxin, capsaicin, L-N G-nitro arginine (L-NNA), and glibenclamide were used to determine mechanisms. L-cysteine (10 -4-10 -2M; substrate for H 2S production) and aminooxyacetic acid and DL-propargylglycine (inhibitors of enzymes generating H 2S endogenously) were used to study endogenous production. Aminooxyacetic acid, DL-propargylglycine, L-NNA, and vasoactive intestinal polypeptide (VIP) antagonist [D-p-Cl-Phe 6,Leu 17]-VIP were used to study H 2S release during electrical field stimulation (EFS) and interaction with VIP and nitric oxide. Immunohistofluorescence of jejunal whole mounts was performed for endogenous H 2S-producing enzymes. Results: Cystathionine-β-synthase and cystathionine-γ-lyase were expressed only in myenteric plexus. NaHS suppressed spontaneous and stimulated contractile activity (P < 0.01). Glibenclamide prevented some suppression by NaHS (P = 0.01) of stimulated contractile activity but did not prevent suppression of spontaneous contractile activity. Other drugs had no effect on spontaneous contractile activity but increased inhibitory effects of NaHS on spontaneous and stimulated contractile activity (P < 0.05). L-cysteine had no effects on contractile activity. Inhibitors altered basal and stimulated activity suggesting endogenous release of H 2S. Conclusions: H 2S presumably suppresses contractile activity in jejunum by direct effects on smooth muscle. Mechanism(s) of inhibition remains unclear, because blocking known neurotransmitters enhanced H 2S-induced suppression, while blocking adenosine triphosphate (ATP)-sensitive K +-channels did not block H 2S-induced inhibition.
AB - Background: Effects of hydrogen sulfide (H 2S), a third gasotransmitter of the gut, are not well understood. The aim of this study was to determine effects/mechanisms of H 2S action on contractile function in rat jejunal muscle. Methods: Transmural strips of longitudinal muscle were evaluated. Response to sodium hydrosulfide (NaHS, H 2S donor; 10 -5-10 -3M) was studied on spontaneous contractile activity and after precontraction (bethanechol, 3 × 10 -6M). Atropine, propranolol, phentolamine, tetrodotoxin, capsaicin, L-N G-nitro arginine (L-NNA), and glibenclamide were used to determine mechanisms. L-cysteine (10 -4-10 -2M; substrate for H 2S production) and aminooxyacetic acid and DL-propargylglycine (inhibitors of enzymes generating H 2S endogenously) were used to study endogenous production. Aminooxyacetic acid, DL-propargylglycine, L-NNA, and vasoactive intestinal polypeptide (VIP) antagonist [D-p-Cl-Phe 6,Leu 17]-VIP were used to study H 2S release during electrical field stimulation (EFS) and interaction with VIP and nitric oxide. Immunohistofluorescence of jejunal whole mounts was performed for endogenous H 2S-producing enzymes. Results: Cystathionine-β-synthase and cystathionine-γ-lyase were expressed only in myenteric plexus. NaHS suppressed spontaneous and stimulated contractile activity (P < 0.01). Glibenclamide prevented some suppression by NaHS (P = 0.01) of stimulated contractile activity but did not prevent suppression of spontaneous contractile activity. Other drugs had no effect on spontaneous contractile activity but increased inhibitory effects of NaHS on spontaneous and stimulated contractile activity (P < 0.05). L-cysteine had no effects on contractile activity. Inhibitors altered basal and stimulated activity suggesting endogenous release of H 2S. Conclusions: H 2S presumably suppresses contractile activity in jejunum by direct effects on smooth muscle. Mechanism(s) of inhibition remains unclear, because blocking known neurotransmitters enhanced H 2S-induced suppression, while blocking adenosine triphosphate (ATP)-sensitive K +-channels did not block H 2S-induced inhibition.
KW - ATP-sensitive K -channels
KW - enteric nervous system
KW - hydrogen sulfide
KW - motility
KW - primary afferent nerve fibers
KW - small intestine
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U2 - 10.1016/j.jss.2011.03.069
DO - 10.1016/j.jss.2011.03.069
M3 - Article
C2 - 21571312
AN - SCOPUS:84860756004
SN - 0022-4804
VL - 175
SP - 234
EP - 242
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -