Abstract
Hydrogen sulfide (H2S) is known for its characteristic odour of "rotten eggs" besides its hazard deposition. One of the major targets for chronic exposure to H2S is the lung where it has been reported that capsaicin-sensitive sensory nerves may serve to protect (Prior, M. et al Toxicol Pathol 1990;18:279-88). Even so H2S is endogenously generated in the body with relatively high levels reported in the brain (˜160 μM) and blood (˜100 μM) (Wang, R. FASEBJ 2002;16:1792-8). We found that H2S contracted isolated guinea pig bronchi and as a consequence our aim was to define if H2S could modulate TRPV1. Bronchial rings were removed and placed in 5ml organ baths containing oxygenated Krebs buffer (37°C) at a resting tension of 1.5g. After an initial stabilisation period (90 min) tissues were contracted with and results expressed as % carbachol (CCh 1 μM). To examine the effect of H2S we chose NaHS, as a salt it easily reacts with water to give H2S and OH. NaHS (10 μM – 30 mM) produced a concentration-dependent contractile response (10 mM) (85 ± 11 %, n = 13) that was significantly attenuated after capsaicin desensitisation (-14 ± 10 %, n = 4), pre-treatment by capsazepine (CPZ) TRPV1 antagonist (3 ± 14 %, n = 6), and by a combination of NK1 (SR140333) and NK2 (SR48968) receptor antagonists (-6 ± 2 %, n = 4). CPZ (10 μM) reduced by 78% the capsaicin response (0.1 μM), but had no effect on SP (1 μM) or CCh (1 μM). The findings indicate that not only chronic exposure but also concentrations not dissimilar to endogenous levels of H2S are capable of evoking the release of tachykinins and bronchial contraction via TRPV1 activation.