ANGIOTENSIN-RESPONSIVE ADRENAL GLOMERULOSA CELL-PROTEINS - CHARACTERIZATION BY PROTEASE MAPPING, SPECIES COMPARISON, AND SPECIFIC ANGIOTENSIN RECEPTOR ANTAGONISTS

Angiotensin II (AngII)-stimulated aldosterone synthesis is mediated by the AngII type 1 (AT(1)) receptor and requires ongoing protein synthe sis. Hormonally-stimulated turnover of a family of 28- to 30-kDa prote ins (p30, or steroidogenic acute regulatory proteins) has been linked to enhanced steroid synthesis in several tissues. Our previous work sh owed that AngII, dibutyryl cAMP, potassium, and atrial natriuretic pep tide affected labeling of a group of eight proteins (four of 28 kDa an d four of 30 kDa) in bovine adrenal glomerulosa cells. This report ext ends our findings in three ways: I) The eight [S-35]-methionine-labele d p30 proteins in bovine cells were compared with each other by chymot ryptic peptide mapping. Similarity in maps indicated that the eight pr oteins share a common primary structure. 2)Dibutyryl cAMP treatment of rat adrenal glomerulosa cells affected the levels of Four 28-kDa prot eins and one 35-kDa protein, whereas AngII affected two of the 28-kDa proteins. There were no responsive 80-kDa proteins in rats comparable with those seen in bovine cells. These results indicate a species diff erence in the affected proteins. 3) The AT(1) receptor antagonist, los artan, inhibited the effects of AngII on aldosterone synthesis and tur nover of the p30 proteins in bovine adrenal glomerulosa cells. PD12331 9, an antagonist specific for the AngII type 2 receptor, did not block AngII-stimulated aldosterone synthesis and had much less effect on p3 0 protein labeling than did losartan. These results add to the growing body of evidence that this family of p30 or steroidogenic acute regul atory proteins plays a role in the acute regulation of steroidogenesis by a wide variety of stimulatory hormones in several tissues and spec ies. In addition, Iosartan's inhibition of AngII's effects on the p30 proteins is consistent with a key role for these proteins in processes linking occupation of the AT, receptor to stimulation of aldosterone synthesis.