ENDOTHELIN-CONVERTING ENZYME IN HUMAN TISSUES

Our aim was to determine whether the expression of endothelin-converti ng enzyme in human tissues would correlate with the distribution of it s substrate, big endothelin-1, and its product, the mature peptide. Si te-directed antisera raised against the conserved C-terminus of the ma mmalian enzyme were used to measure the immunoreactive enzyme in micro somal fractions prepared from tissue homogenates and to localize stain ing to the endothelial cells lining large conduit and smaller resistan ce vessels within cardiac, adrenal, respiratory and brain tissue. The activity of endothelin-converting enzyme was measured and characterize d in isolated endothelial cells. This pattern of staining in the vascu lar endothelium paralleled that of mature endothelin and big endotheli n-1, and these peptides were detectable by radioimmunoassay in all tis sues examined. Immunoreactive endothelin-converting enzyme localized t o other cell types, including bronchial epithelial cells, and to fibre s within the glial limitans, neuronal processes and cell bodies of the cerebral cortex. Although perivascular astrocytes in the subcortical white matter displayed intense endothelin-converting enzyme-like immun oreactivity, endothelin staining was not detected. The results suggest that endothelin-converting enzyme has a ubiquitous distribution withi n the human vascular endothelium and is positioned to catalyse the con version of big endothelin-1 to the biologically active endothelin-1, w hich on release may contribute to the maintenance of basal tone in hum ans. Endothelin-converting enzyme localized to epithelial cells in per ipheral tissues or astrocytes within the brain may be upregulated in p athophysiological conditions in which endothelin levels are increased and could represent a further target for therapeutic intervention by e nzyme inhibitors. (C) 1998 Chapman & Hall.