Abstract 217: Angiotensin II Stimulates Renin Synthesis and Secretion in Mouse Collecting Duct M-1 Cells via a PKCα-mediated cAMP Stimulation Mechanism

Angiotensin (Ang) II stimulates renin synthesis and secretion in collecting duct (CD) cells; via the Ang II type 1 receptor (AT1R), an effect that is in contrast to the well-known inhibition that it exerts on juxtaglomerular apparatus (JGA) renin. However, the intracellular signaling mechanisms involved in the Ang II-mediated stimulation of renin synthesis and secretion by the principal cells of the CD have not been elucidated. We recently demonstrated that Ang II increases renin synthesis via protein kinase C (PKC) in primary cultured rat IMCD cells. Additionally, we found that Ang II increases intracellular cAMP levels in IMCD cells, suggesting that in CD cells, PKA/CREB might be the downstream target of cAMP. In the present study, we used a mouse cortical CD cell line (M-1) to determine the role of the cAMP/PKA/CREB pathway in the stimulation of the Ang II-mediated renin synthesis and secretion by the principal cells, and to examine the role of PKC in the stimulation of cAMP levels in this mechanism. In M-1 cells, Ang II (10-7 M) treatment increased renin mRNA and protein levels. Renin content measured in the cell culture media was augmented in Ang II-treated cells by 6 hrs (Ang II: 31±4 vs. 19±4 ng Ang I/hr/ml; p