Abstract
Purpose:
We have evidence that hydrogen sulfide ( H2S) donors such as sodium hydrosulfide (NaHS) can produce pharmacological actions on isolated porcine ocular smooth muscles. In this study, we investigated the pharmacological effects of L-cysteine, a substrate for H2S production, on isolated pre-contracted bovine ciliary muscle.
Methods:
Isolated bovine ciliary muscle strips were set up in organ baths containing oxygenated Krebs buffer (pH 7.4) at 37°C. Changes in longitudinal isometric tension were recorded via grass FT03 Force-displacement transducers and analyzed using PolyView software. Effects of L-cysteine on carbachol-induced tone was studied in the presence of enzyme inhibitors for H2S biosynthetic pathway (AOA; cystathionine β-synthase inhibitor) and prostanoids (flurbiprofen; cyclo-oxygenase (COX) inhibitor).
Results:
L-cysteine (0.01 nM-100 µM) evoked a concentration-dependent relaxation of carbachol-induced tone in bovine ciliary muscle, reaching a maximum inhibition of 88% at 10 µM (with an IC50 of 2 nM). Relaxations elicited by L-cysteine were unaffected by pre-treatment of tissues with flurbiprofen (3 μM). The inhibitor of cystathionine β-synthase, AOA (10 µM) blocked only relaxations caused by high concentrations of L-cysteine (> 500 nM).
Conclusions:
L-cysteine can relax pre-contracted bovine ciliary muscle, and this effect is dependent on endogenous production of H2S. Furthermore, prostanoids are not involved in the inhibitory action of L-cysteine in this smooth muscle.
Keywords: 456 ciliary muscle •
616 neurotransmitters/neurotransmitter systems •
514 enzymes/enzyme inhibitors