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 microinjectio n needle, the dopamine release from the striatum dose-dependently incr eased. Pretreatment with a glutamate receptor blocker, glutamate dieth yl ester hydrochloride, inhibited the dopamine release induced by ET-3 , whereas it further enhanced the dopamine release by ET-1. This sugge sts that ET-1 directly induces the dopamine release, whereas the actio n of ET-3 is mediated by glutamate different distributions of endothel in receptors: ET(A) receptors may be present on the dopaminergic neuro ns, but ET(B) receptors on the glutamatergic neurons.