Role of hydrogen sulfide production in inhibitory action of L-cysteine on isolated porcine irides
| Autor: | Ghislaine Kouamou, Catherine A. Opere, Ya Fatou Njie-Mbye, Angela M. LeDay, Emmanuel Monjok, Sunny E. Ohia |
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| Rok vydání: | 2010 |
| Předmět: |
Swine
Muscle Relaxation Cystathionine beta-Synthase Iris Stimulation Cholinergic Agonists Inhibitory postsynaptic potential Glibenclamide Cellular and Molecular Neuroscience KATP Channels Isometric Contraction Muscarinic acetylcholine receptor Glyburide medicine Animals Cysteine Hydrogen Sulfide Receptor chemistry.chemical_classification Dose-Response Relationship Drug Antagonist Cystathionine gamma-Lyase Muscle Smooth Receptors Muscarinic Sensory Systems Ophthalmology Enzyme chemistry Mechanism of action Biochemistry Biophysics Carbachol medicine.symptom medicine.drug |
| Zdroj: | Current eye research. 35(5) |
| ISSN: | 1460-2202 |
| Popis: | To investigate the direct pharmacological actions of L-cysteine, a substrate for the production of H(2)S, 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.Isolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution at 37 degrees 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 H(2)S, and prostanoids. In addition, we also examined the effect of ATP-sensitive K(+) (K(ATP)) channel antagonist, glibenclamide on relaxations induced by L-cysteine.L-cysteine (30 nM-1 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 (P0.001) in the presence of the COX inhibitor, flurbiprofen (3 microM). Additionally,in the presence of flurbiprofen, the H(2)S donors, NaHS and Na(2)S, mimicked the relaxations produced by L-cysteine, yielding IC(50) values of 5.8 microM and 180 microM, respectively. Both the inhibitor of cystathionine beta-synthase, AOA (30 microM) and the K(ATP) channel antagonist, glibenclamide (100 microM) caused significant (P0.001) rightward shifts in the concentration-response curves to L-cysteine and attenuated the maximum inhibitory response. Conversely, the inhibitor of cystathionine gamma-lyase, PAG (1 mM) blocked only relaxations caused by high concentrations of L-cysteine (100 microM).The inhibitory action of L-cysteine in isolated porcine irides is dependent on the endogenous production of H(2)S by cystathionine gamma-lyase and cystathionine beta-synthase. Furthermore, prostanoids and K(ATP) channels are involved in the inhibitory action of L-cysteine in this tissue. |
| Databáze: | OpenAIRE |
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