Endothelin ETA- and ETB-Receptor-Mediated Inhibition of Noradrenaline Release From Isolated Rat Stomach

Abstract

We examined the effect of endothelin-1, endothelin-3 and sarafotoxin S6c on the release of noradrenaline from gastric sympathetic nerve terminals using an isolated, vascularly perfused rat stomach. The release of noradrenaline evoked by electrical stimulation of the gastric postganglionic sympathetic nerves (at 2.5 Hz for 1 min) was inhibited by endothelin-1 (10-10 – 10-8 M), endothelin-3 (10-9 – 10-8 M) and sarafotoxin S6c (a highly selective agonist of endothelin ETB receptors) (10-9 – 10-8 M) in a concentration-dependent manner; the inhibitory potencies were as follows: endothelin-1 > endothelin-3 > sarafotoxin S6c. The inhibitory effect of endothelin-1 (3 × 10-9 M) on noradrenaline release was abolished by BQ-123 (a selective antagonist of endothelin ETA receptors) in a dose-dependent manner (10-7 and 10-6 M), but not influenced by BQ-788 (a selective antagonist of endothelin ETB receptors) (10-7 and 10-6 M). The endothelin-1-induced inhibition of noradrenaline release was attenuated by pretreatment with pertussis toxin (10 μg/animal, i.v., 4 days before experiments), but not influenced by indomethacin (3 × 10-6 M). These results indicate that endothelin ETA and ETB receptors located on the sympathetic nerve terminals play a role in the inhibition of noradrenaline release from the rat stomach: endothelin ETA receptor-mediated inhibition is carried out by pertussis toxin-sensitive and indomethacin-insensitive mechanisms.