title: Angiotensin II receptors and in vitro aldosterone responses of aldosterone-producing adenomas, adjacent nontumorous tissue, and normal human adrenal glomerulosa.
abstract: Angiotensin II (angio II) receptors have been compared using tissues from aldosterone-producing adenomas (APAs), adjacent nontumorus tissue, and normal human adrenal glomerulosa. Plasma membrane-rich subcellular fractions were employed in a radioreceptor assay with [125I]angio II. In vitro aldosterone secretory response to angio II were determined using isolated cells obtained by collagenase digestion. Results are reported as the mean +/- SE. Normal glands have high and low affinity receptor sites for angio II. The Ka values for a normal adrenal obtained at surgery were 2.5 and 0.4 nM-1, while autopsy adrenals were 1.1 +/- 0.4 and 0.3 +/- 0.15 nM-1 (n = 3). APAs and adjacent nontumorous tissue possessed only low affinity receptor sites (0.22 +/- 0.05 nM--1; n = 11). The receptor concentration for a surgically obtained adrenal was 1562 fmol/mg protein, contrasted with 466 +/- 135 from autopsy adrenals. APA and adjacent tissue bound 462 +/- 112 fmol/mg protein. Cells from seven of eight APAs produced aldosterone when stimulated by angio II (3 x 10(-10)-10(-6) m). The increments were 16-105% above basal levels. The response were similar to but less senstive than cells from normal adrenals. The only tumor that failed to respond had 1/50th of the receptors of the other APAs. In contrast, only three of seven adjacent tissues responded, and then only negligibly. ACTH (10(-8) M) increased aldosterone production by APAs 10-158%, by normal cells 283% and by three of six adjacent nontumorous tissues 170-400%. The observations that APAs have angio II receptors and aldosterone responses to angio II is consistent with the fact that some patients with APA have postural increments of plasma posture. The presence of receptors of adjacent tissue and no in vitro response suggest a defect in the aldosterone biosynthetic pathway as a cause of the prolonged absence of response to angio II after removal of APAs.
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone