Endothelin-1 and endothelin-3 modulate dopaminergic neurons through different mechanisms.

Novel vasoconstrictor peptides, endothelin-1 (ET-1) and endothelin-3 (ET-3), are also known as neuropeptides or neuromodulators. When either ET-1 or ET-3 was administered to the rat striatum via a microinjection needle, the dopamine release from the striatum dose-dependently increased. Pretreatment with a glutamate receptor blocker, glutamate diethyl ester hydrochloride, inhibited the dopamine release induced by ET-3, whereas it further enhanced the dopamine release by ET-1. This suggests that ET-1 directly induces the dopamine release, whereas the action of ET-3 is mediated by glutamate receptors. We postulate that this difference may result from the different distributions of endothelin receptors: ETA receptors may be present on the dopaminergic neurons, but ETB receptors on the glutamatergic neurons.