Angiotensin III Stimulates ERK1/2 Mitogen-Activated Protein Kinases and Astrocyte Growth in RatAstrocytes

Objective. We investigated in astrocytes whether Ang III stimulates ERK1/2 mitogen activated protein kinases (MAPK) and astrocyte growth. Background. Angiotensin (Ang) III is a biologically peptide with similar effects and receptor binding properties as Ang II. Most studies delineate physiological effects of the peptide, but the intracellular pathways leading to the actions are unknown and are a focus of these studies. Methods. Gel electrophoresis and Western blotting techniques were used to determine Ang III JNK MAPK effects. 3H-Thymidine incorporation was used to determine astrocyte growth. Results. Ang III stimulated ERK1/2 MAPK in a dose- and time-dependent manner. Maximal stimulation occurred with 100 nM Ang III. This stimulation occurred as early as 1 minute, and was sustained for at least 15 minutes. The ERK1/2 MAPK inhibitor PD98059 attenuated Ang III-induced ERK1/2 phosphorylation. The Ang AT1 receptor inhibitor, Losartan, prevented Ang III-induced ERK1/2 phosphorylation while the selective AT2 Ang receptor blocker PD123319 was ineffective. Ang III stimulated astrocyte growth in a concentrationdependent manner, an effect that occurred via activation of the AT1 receptor as well. These findings suggest that Ang III has similar effects as Ang II in astrocytes since it rapidly stimulates the phosphorylation of the ERK1/2 MAPK and induces astrocyte proliferation through activation of the AT1 receptor. These studies are important in establishing signaling pathways for Ang III and provide validation of the central role of Ang III. Grants. This study was supported by a President's Faculty Research and Development Grant.