ENDOTHELIN INCREASED [CA2+](I) IN CULTURED NEURONS AND SLICED OF RAT HIPPOCAMPUS

WE reported here the first evidence that endothelin (ET)-1 and ET-3 produced an increase in intracellular Ca2+ concentrations ([Ca2+](1)), consisting of a transient and a sustained component, in cultured neurones and in slices of the rat hippocampus. In the neurones, the removal of Ca2+ or the addition of Cd2+ remarkably inhibited the ET-3-evoked sustained but not the transient response. The [Ca2+](i) increased by ETs was observed in the dentate gyrus and in the vicinity of CA1 and CA3 pyramidal cell layer in the hippocampus, findings in good accord with regions where the glutamate receptor agonists have an elevated [Ca2+](i). The possible causal link between ETs and the increased [Ca2+](i) in the development of hippocampal neuronal death is discussed.