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 associated with behaviour and neuroendocrine regulation as well as cardiovascular control. We review the evidence for an interaction of endothelin with brain dopaminergic mechanisms. Our work has shown that particularly endothelin-1 and ET(B) receptors are present at significant levels in typical brain dopaminergic regions such as the striatum. Moreover, lesion studies showed that ET(B) receptors are present on dopaminergic neuronal terminals in striatum and studies with local administration of endothelins into the ventral striatum showed that activation of these receptors causes dopamine release, as measured 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 ET(A) receptors, we propose that physiological levels of these peptides play an important role in normal brain function, at least partly by interacting with dopamine release through ET(B) receptors.