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E. Monjok, G.E. Kouamou, C.A. Opere, S.E. Ohia; Further Studies on the Pharmacological Actions of Hydrogen Sulfide on Isolated Porcine Irides . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2612.
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In a previous study, we showed that the hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) can produce relaxations of isolate porcine irides and that this effect is partly mediated through KATP channels (Monjok et al., IOVS 46: E–Abstract 3684, 2005.).
In the present study, we investigated the role of two biosynthetic enzymes of H2S (cystathionine γ–lyase and cystathionine ß–synthase) in the inhibitory response elicited by this gas (using NaHS as H2S donor) on carbachol–induced contractions in isolated porcine irides. Furthermore, we examined the role of nitric oxide in the relaxations caused by this gas in porcine irides, in vitro.
Isolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution at 37oC. Longitudinal isometric tension was recorded via a grass FT03 Force–displacement Transducers and analyzed using the PolyView computer software. An initial load of 150 mg was placed on each tissue after which they were allowed to equilibrate for one hour. The relaxant action of NaHS on carbachol–induced tone was studied in the absence and presence of an inhibitor of cystathionine γ–lyase (ß–cyanoalanine, BCA), an activator of cystathionine ß–synthase (S–adenosyl–L–methionine,SAM) and an inhibitor of nitric oxide synthase (L–nitroarginine methyl ester, L–NAME) .
NaHS (30 nM – 300 µM) produced concentration–dependent relaxations of carbachol–induced tone. The inhibitor of cystathionine γ–lyase, BCA (1 mM) caused significant (P < 0.001) rightward shifts in the concentration–response curves to NaHS. In contrast, the nitric oxide synthase inhibitor, L–NAME had no significant (P > 0.05) effect on the relaxations induced by NaHS. The activator of cystathionine ß–synthase, SAM (100 µM) enhanced relaxations elicited by low concentrations of NaHS (less than 3 µM) but attenuated responses cause by the higher concentrations of this H2S donor.
The observed inhibitory action of NaHS in isolated porcine irides is dependent on endogenous biosynthesis of H2S by cystathionine γ–lyase and cystathionine ß–synthase. Furthermore, nitric oxide is not involved in the relaxations induced by this gas in the isolated porcine irides.
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