INTERNALIZATION OF THE TYPE-I ANGIOTENSIN-II RECEPTOR (AT1) AND ANGIOTENSIN-II FUNCTION IN THE RAT ADRENAL ZONA GLOMERULOSA CELL

Using a specific monoclonal antibody (6313/G2) to the first extracellu lar domain of the type 1 receptor (AT1), we showed that most of the re ceptor is internalised in the rat glomerulosa cell. When viable glomer ulosa cells are incubated with 6313/G2, the receptor is transiently co ncentrated on the cell surface, and aldosterone output is stimulated. This stimulated output is enhanced by neither threshold nor maximal st imulatory 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 intrinsi c action on protein kinase C (PKC) activation, it significantly inhibi ts 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 protei n interaction to generate maximal steroidogenic effects, through IP3 g eneration. PKC activation induced by angiotensin II has no bearing on steroidogenesis in the dispersed glomerulosa cell system.