{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:15:55Z","timestamp":1789848955316,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T00:00:00Z","timestamp":1504483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK\u201028300"],"award-info":[{"award-number":["DK\u201028300"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) plays an important role in smooth muscle relaxation. Here, we investigated the expression of enzymes in H<jats:sub>2<\/jats:sub>S synthesis and the mechanism regulating colonic smooth muscle function by H<jats:sub>2<\/jats:sub>S. Expression of cystathionine\u2010\u03b3\u2010lyase (CSE), but not cystathionine\u2010\u03b2\u2010synthase (CBS), was identified in the colonic smooth muscle of rabbit, mouse, and human. Carbachol (CCh)\u2010induced contraction in rabbit muscle strips and isolated muscle cells was inhibited by <jats:sc>l<\/jats:sc>\u2010cysteine (substrate of CSE) and NaHS (an exogenous H<jats:sub>2<\/jats:sub>S donor) in a concentration\u2010dependent fashion. H<jats:sub>2<\/jats:sub>S induced S\u2010sulfhydration of RhoA that was associated with inhibition of RhoA activity. CCh\u2010induced Rho kinase activity also was inhibited by <jats:sc>l<\/jats:sc>\u2010cysteine and NaHS in a concentration\u2010dependent fashion. Inhibition of CCh\u2010induced contraction by <jats:sc>l<\/jats:sc>\u2010cysteine was blocked by the CSE inhibitor, <jats:sc>dl<\/jats:sc>\u2010propargylglycine (DL\u2010PPG) in dispersed muscle cells. Inhibition of CCh\u2010induced Rho kinase activity by <jats:sc>l<\/jats:sc>\u2010cysteine was blocked by CSE siRNA in cultured cells and DL\u2010PPG in dispersed muscle cells. Stimulation of Rho kinase activity and muscle contraction in response to CCh was also inhibited by <jats:sc>l<\/jats:sc>\u2010cysteine or NaHS in colonic muscle cells from mouse and human. Collectively, our studies identified the expression of CSE in colonic smooth muscle and determined that sulfhydration of RhoA by H<jats:sub>2<\/jats:sub>S leads to inhibition of RhoA and Rho kinase activities and muscle contraction. The mechanism identified may provide novel therapeutic approaches to mitigate gastrointestinal motility disorders.<\/jats:p>","DOI":"10.1002\/prp2.343","type":"journal-article","created":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T07:26:37Z","timestamp":1504509997000},"source":"Crossref","is-referenced-by-count":18,"title":["Inhibition of RhoA\/Rho kinase pathway and smooth muscle contraction by hydrogen sulfide"],"prefix":"10.1002","volume":"5","author":[{"given":"Ancy D.","family":"Nalli","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics VCU Program in Enteric Neuromuscular Sciences Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics VCU Program in Enteric Neuromuscular Sciences Virginia Commonwealth University Richmond 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