Internalisation of the type 1 angiotensin II receptor (AT1) and angiotensin II function in the rat adrenal zona glomerulosa cell.

Abstract

Using a specific monoclonal antibody (6313/G2) to the first extracellular domain of the type 1 receptor (AT1), we showed that most of the receptor is internalised in the rat glomerulosa cell. 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, it 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.