DIFFERENTIAL DISTRIBUTION OF ENDOTHELIN PEPTIDES AND RECEPTORS IN HUMAN ADRENAL-GLAND

Sub-type selective ligands revealed a differential distribution of end othelin (ET) receptors within human adrenal glands. High densities of ET(A) receptors were localized, using [I-125]-PD151242, to the smooth muscle layer of the arteries, smaller vessels within the capsular plex us and to the secretory cells of zona glomerulosa (K-D=139.8 +/- 39.7, B-max=69.7 +/- 9.1 fmol mg(-1) protein, mean of 3 individuals +/- sem ). ET(B) receptors were present in the medulla (K-D=145.2 +/- 16.4, B- max=75.5 +/- 12.3), zona glomerulosa (K-D=100.6 +/- 35.1, B-max=63.1 /- 10.0), fasiculata (K-D 145.1 +/- 16.2, B-max=679 +/- 6.9) and retic ularis (K-D=118.2 +/- 18.6, B-max=71.9 +/- 6.5). ET(B) receptors were not detected within the smooth muscle of the vasculature. Messenger RN A encoding both sub-types was present in adrenals. ET-like immunoreact ivity was localized to the cytoplasm of the endothelial cells from art eries supplying the gland and resistance vessels within the capsular p lexus. Staining was also detected in these cells using anti-big ET-1 a nd less intensely with anti-big ET-2 antisera but not within cells wit hin the cortex or medulla. Big ET-3-like immunoreactivity was localize d to secretory cells of the medulla. Staining was not found using anti serum that could detect ET-3, suggesting further processing of big ET- 3 may occur within the plasma, and that the adrenals could be a source of ET-3. The presence of ET-1 was confirmed by high performance liqui d chromatography and radioimmunoassay although ET-3 was not detected. The results suggest that ET-1 is the predominant mature isoform, which is localized mainly to adrenal, vasculature, particularly the capsula r plexus, and may contribute to blood flow regulation in the gland.