Expression of the Potent Vasoconstrictor Endothelin

Endothelin is a potent vasoconstrictive peptide initially characterized as a product of endothelial cells. To examine the potential role of endothelin as a neuropeptide, we studied its distribution in the human central nervous system. RNA blot hybridization provided evidence of endothelin gene transcription in a variety of functional regions of the brain. In situ hybridization confirmed the widespread pattern of endothelin transcription and indicated that the highest density of cells containing endothelin mRNA is in the hypothalamus. This technique localized endothelin transcription to cells of the nervous system as well as the vascular endothelium. Immunocytochemical studies detected endothelin immunoreactivity in neurons, providing evidence of the synthesis of the peptide in this cell type and confirming that endothelin is a neuropeptide. Although the prominent expression of endothelin in the hypothalamus may indicate a central vasoregulatory role for the peptide, the widespread distribution of endothelin in neurons in other areas of the brain implies a more fundamental role in the regulation of nervous system function. (J. Clin. Invest. 1990. 86:141-147.)