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

Research output: Contribution to journalArticle

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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
StatePublished - May 2010

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Hydrogen Sulfide
Iris
Cysteine
Swine
Cystathionine
Carbachol
Prostaglandins
Adenosine Triphosphate
KATP Channels
Lyases
Glyburide
Biosynthetic Pathways
Enzyme Inhibitors
Muscarinic Receptors
Poaceae
Transducers
Baths
Smooth Muscle
Buffers
Software

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Role of hydrogen sulfide production in inhibitory action of L-cysteine on isolated porcine irides. / Ohia, Sunny E.; Opere, Catherine A.; Monjok, Emmanuel M.; Kouamou, Ghislaine; Leday, Angela M.; Njie-Mbye, Ya Fatou.

In: Current Eye Research, Vol. 35, No. 5, 05.2010, p. 402-407.

Research output: Contribution to journalArticle

Ohia, Sunny E. ; Opere, Catherine A. ; Monjok, Emmanuel M. ; Kouamou, Ghislaine ; Leday, Angela M. ; Njie-Mbye, Ya Fatou. / Role of hydrogen sulfide production in inhibitory action of L-cysteine on isolated porcine irides. In: Current Eye Research. 2010 ; Vol. 35, No. 5. pp. 402-407.
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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.",
author = "Ohia, {Sunny E.} and Opere, {Catherine A.} and Monjok, {Emmanuel M.} and Ghislaine Kouamou and Leday, {Angela M.} and Njie-Mbye, {Ya Fatou}",
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T1 - Role of hydrogen sulfide production in inhibitory action of L-cysteine on isolated porcine irides

AU - Ohia, Sunny E.

AU - Opere, Catherine A.

AU - Monjok, Emmanuel M.

AU - Kouamou, Ghislaine

AU - Leday, Angela M.

AU - Njie-Mbye, Ya Fatou

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

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