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Enhanced relaxant effect of Sodium Hydrogen Sulfide (NaHS) in Experimental Colitis and its action on KATP Channels via S‐sulfhydration
Author(s) -
Kang Minho,
Gade Aravind,
Akbarali Hamid I
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1048.14
Subject(s) - chemistry , colitis , sodium hydrosulfide , hydrogen sulfide , pharmacology , muscle relaxation , potassium channel , biophysics , biochemistry , endocrinology , medicine , biology , sulfur , organic chemistry
Hydrogen sulfide (H 2 S) has recently been recognized as a gaseous signaling molecule that affects smooth muscle function. The aim of this study was to determine the effect of inflammation on the responses to H 2 S in smooth muscle of mouse colon. Colonic inflammation was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) in BALB/C mice. Isometric force was measured in the organ bath. In carbachol‐precontracted tissues, levcromakalim (LEV), a K ATP channel opener, induced dose‐dependent relaxations (IC 50 1036 nM, n=5). The dose‐response was shifted to the left in inflamed colon (IC 50 458 nM, n=6). Similarly, relaxations to NaHS were also shifted to the left in the colitis model (control IC 50 196 μM, n=6: inflamed IC 50 151 μM, n=3) and maximal amplitude of relaxation was enhanced by 40%. Pretreatment with glybenclamide (100 uM) abolished LEV relaxations and reduced NaHS relaxations by 46 ± 8.2% (n=3). A Biotin switch assay was performed to determine s‐sulfyhdyration of SUR2B subunit of K ATP . NaHS significantly enhanced sulfhyrdration of SUR2B in CHO transfected cells and in native colonic tissues. These data suggest that enhanced hydrogen sulfide during colitis, regulates contractile activity in the smooth muscle of mouse colon through S‐sulfhydration of the K ATP channel. Supported by NIH DK046367.