Role of hydrogen sulfide production in inhibitory action of L-cysteine on isolated porcine irides

Sunny E. Ohia, Catherine A. Opere, Emmanuel M. Monjok, Ghislaine Kouamou, Angela M. Leday, Ya Fatou Njie-Mbye

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14 Scopus citations

Abstract

Purpose: To investigate the direct pharmacological actions of L-cysteine, a substrate for the production of H2S, on isolated porcine irides in the presence of tone induced by muscarinic receptor stimulation. Furthermore, we examined the underlying mechanism of action of L-cysteine in this smooth muscle. Methods: Isolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution at 37°C. Longitudinal isometric tension was recorded via a grass FT03 Force-Displacement Transducer and analyzed using the PolyView computer software. The relaxant action of L-cysteine on carbachol-induced tone was studied in the absence and presence of inhibitors of enzymes of the biosynthetic pathways for H2S, and prostanoids. In addition, we also examined the effect of ATP-sensitive K+ (K ATP) channel antagonist, glibenclamide on relaxations induced by L-cysteine. Results: L-cysteine (30 nM1 mM) evoked concentration-dependent relaxations of carbachol-induced tone in isolated porcine irides, reaching a maximum inhibition of 43% at 1 mM. This response was enhanced significantly (P <0.001) in the presence of the COX inhibitor, flurbiprofen (3 μM). Additionally,in the presence of flurbiprofen, the H2S donors, NaHS and Na2S, mimicked the relaxations produced by L-cysteine, yielding IC50 values of 5.8 μM and 180 μM, espectively. Both the inhibitor of cystathionine β-synthase, AOA (30 μM) and the K ATP channel antagonist, glibenclamide (100 μM) caused significant (P <0.001) rightward shifts in the concentration-response curves to L-cysteine and attenuated the maximum inhibitory response. Conversely, the inhibitor of cystathionine γ-lyase, PAG (1 mM) blocked only relaxations caused by high concentrations of L-cysteine (> 100 μM). Conclusions: The inhibitory action of L-cysteine in isolated porcine irides is dependent on the endogenous production of H2S by cystathionine γ-lyase and cystathionine β-synthase. Furthermore, prostanoids and KATP channels are involved in the inhibitory action of L-cysteine in this tissue.

Original languageEnglish
Pages (from-to)402-407
Number of pages6
JournalCurrent Eye Research
Volume35
Issue number5
DOIs
Publication statusPublished - May 2010

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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