Inhibition of RhoA-dependent pathway and contraction by endogenous hydrogen sulfide in rabbit gastric smooth muscle cells.

摘要: Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, increase cyclic nucleotide levels inhibit muscle contraction via inhibition of myosin light chain (MLC) kinase activation MLC phosphatase (MLCP). H2S produced as an endogenous signaling molecule synthesized mainly from l-cysteine cystathionine-γ-lyase (CSE) cystathionine-β-synthase (CBS) regulates contraction. The aim this study was to analyze the expression CSE function in regulation MLCP activity, 20-kDa regulatory II (MLC20) phosphorylation, isolated gastric smooth cells. Both mRNA protein CSE, but not CBS, were detected cells rabbit, human, mouse stomach. l-cysteine, activator NaHS, a donor H2S, inhibited carbachol-induced Rho PKC kinase-sensitive phosphorylation MYPT1, PKC-sensitive CPI-17, MLC20 sustained inhibitory effects blocked upon suppression by siRNA or its activity dl-propargylglycine (PPG) suggesting that effect is mediated CSE. Glibenclamide, inhibitor KATP channels, had no on H2S. NaHS basal cAMP cGMP augmented forskolin-induced SNP-induced formation. We conclude both exogenous contraction, mechanism involves activities stimulation leading dephosphorylation