The relationship between the adrenal tissue renin-angiotensin system, internalization of the type I angiotensin II receptor (AT1) and angiotensin II function in the rat adrenal zona glomerulosa cell.
Many data suggest that the elements of the tissue renin-angiotensin system (RAS) in the adrenal cortex are mostly located in the zona glomerulosa. The relationship of this paracrine/autocrine system with the cellular localization of the angiotensin II (AII) receptor has not bee clarified. Using a specific monoclonal antibody (6313/G2) to the first extracellular domain of the type 1 receptor (AT1), we show here that most of the receptor is internalized in the rat glomerulosa cell. This may result from tonic stimulation by the tissue RAS, and consequent permanent receptor occupancy. When viable glomerulosa cells are incubated with 6313/G2, the receptor is transiently concentrated on the cell surface, and aldosterone output is stimulated. This stimulated output is enhanced by neither threshold nor maximal stimulatory concentrations of AII amide, although the antibody does not inhibit AII binding to the receptor. The antibody directly stimulates inositol trisphosphate (IP3) generation, but, while having no intrinsic action on protein kinase C (PKC) activation, significantly inhibits the PKC response to angiotensin II. The data suggest that although the receptor is mostly internalized, recycling to the plasma membrane is constitutive, or regulated by unknown factors. Retention of the AT1 receptor in the membrane is alone enough to allow sufficient G protein interaction to generate maximal steroidogenic effects, through IP3 generation. PKC activation induced by angiotensin II has no bearing on steroidogenesis in the dispersed glomerulosa cell system.
D000311:Adrenal Glands / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D007150:Immunohistochemistry; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015384:Zona Glomerulosa / Q000166:cytology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone; D015544:Inositol 1,4,5-Trisphosphate