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Inhibition of RhoA/Rho Kinase Pathway and Contraction by Endogenous and Exogenous Hydrogen Sulfide in Gastrointestinal Smooth Muscle
Author(s) -
Nalli Ancy D,
Rajagopal Senthilkumar,
Mahavadi Sunila,
Grider John R,
Murthy Karnam S
Publication year - 2013
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.27.1_supplement.1164.2
Subject(s) - rhoa , cystathionine beta synthase , chemistry , contraction (grammar) , rho associated protein kinase , endogeny , smooth muscle tissue , vascular smooth muscle , endocrinology , cysteine , medicine , biochemistry , biology , kinase , signal transduction , enzyme , smooth muscle
Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, cause MLC 20 dephosphorylation and smooth muscle relaxation via inhibition of MLCK and activation of MLCP. H 2 S produced by commensal bacteria in the colon or synthesized from L‐cysteine via cystathionine‐γ‐lyase (CSE) and cystathionine‐β‐synthase (CBS) regulates smooth muscle tone. Aim To examine the expression of CSE and CBS in gastrointestinal smooth muscle and to elucidate the molecular mechanism of H 2 S‐induced muscle relaxation. Methods Expression of CSE and CBS was analyzed by RT‐PCR and western blot. The effect of H 2 S on carbachol‐induced muscle contraction and Rho kinase activity was examined using an endogenous activator (L‐cysteine) of CSE and CBS and an exogenous H 2 S donor (NaHS). Results Expression of CSE, but not CBS was detected in smooth muscle cells of stomach and colon from mouse, rabbit and human. Carbachol‐induced contraction in muscle strips and muscle cells, and increase in Rho kinase activity were inhibited by L‐cysteine or NaHS in a concentration‐dependent manner (1 to 100 mM). Glibenclamide, an inhibitor of K ATP channels and a known target of H 2 S, had no effect on the inhibition of contraction by H 2 S. Conclusion Both endogenous and exogenous H 2 S induce muscle relaxation, and the mechanism is via the inhibition of RhoA/Rho kinase activity leading to stimulation of MLCP activity and muscle relaxation.