Endothelin and dopamine release

Endothelins and endothelin receptors are widespread in the brain. There is increasing evidence that endothelins play a role in brain mechanisms associ ated with behaviour and neuroendocrine regulation as well as cardiovascular control. We review the evidence for an interaction of endothelin with brai n dopaminergic mechanisms. Our work has shown that particularly endothelin- 1 and ETB receptors are present at significant levels in typical brain dopa minergic regions such as the striatum. Moreover, lesion studies showed that ETB receptors are present on dopaminergic neuronal terminals in striatum a nd studies with local administration of endothelins into the ventral striat um showed that activation of these receptors causes dopamine release. as me asured both with in vivo voltammetry and behavioural methods. While several previous studies have focussed on the possible role of very high levels of endothelins in ischemic and pathological mechanisms in the brain, possibly mediated by ETA receptors, we propose that physiological levels of these p eptides play an important role in normal brain function, at least partly by interacting with dopamine release through ETB receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.