Characterization of Angiotensin-Mediated ACTH Release

Abstract

The ACTH-releasing activites of angiotensin I, angiotensin III, [des (Asp¹, Arg²)]Ang II, and [des (Asp¹, Arg², VaP³)]Ang II was compared with that of angiotensin II (Ang II) in rat pituitary cell monolayer culture. In addition, the role of known Ang II receptor antagonists, glucocorticoid and of antiadrenergic and antiserotonergic compounds on Ang II induced ACTH release was investigated. The relative potencies of the angiotensin analogs were:Ang II > Ang III > [des (Asp¹, Arg²)]Ang II. [Des (Asp¹, Arg², Val³)]Ang II was nonstimulatory. Angiotensin I-induced ACTH was completely inhibited by the addition of converting enzyme inhibitor SQ2O885. A similar dose-related inhibition of Ang II-stimulated ACTH release by [Sar¹, Ala⁹]Ang II and [Sar¹, Gly⁸]Ang II was demonstrated. Corticosterone (5 nM) decreased Ang II (10 nM) mediated ACTH release to control values while dibenzyline (10 μM), an alpha-adrenergic antagonist and cyproheptadine (10 μM), a serotonin antagonist did not alter the stimulation of ACTH by Ang II. This study suggests (1) the N-terminal amino acids of Ang II are important for the ACTH stimulatory action of Ang II, (2) [Sar¹, Ala⁸]Ang II and [Sar¹, Gly⁸]Ang II are specific Ang II antagonists at the pituitary level towards the ACTH releasing effect of Ang II, and (3) corticosterone inhibits the in vitro pituitary ACTH release by Ang II while dibenzyline and cyproheptadine have no effect.