Endothelin Increases Atrial Natriuretic Peptide Production in Cultured Rat Diencephalic Neurons*

The vasoactive peptides atrial natriuretic peptide (ANP) and endothelin have been localized to several areas of the extravascular brain where they are produced in neurons, often overlapping in distribution. Since endothelin has been found to increase ANP secretion from the heart, we examined a possible regulation by endothelin of the secretion and production of ANP in fetal diencephalic cultures of neurons from gestational day 16 rats. Endothelin produced a concentration-related increase in the secretion of ANP. The ability of endothelin to induce ANP secretion was dependent upon calcium, since added nifedipine, a calcium channel blocker, significantly reversed the effects of this vasoconstrictor peptide. ANP 103-126 was the predominant form secreted, as determined by HPLC followed by RIA. The production of this peptide, assessed by specific mRNA expression, was increased more than 2-fold, in dose-related fashion. These studies provide the first evidence that endothelin regulates ANP gene expression in the brain. Additionally, our secretion studies from neurons are consistent with the known stimulatory effects of endothelin on ANP release from the heart. The regulation of ANP production and secretion by the vasoconstrictor peptide endothelin is one level at which ANP and endothelin might interact in the in vivo brain.