Regulation of Renin Secretion and Renin Synthesis by Second Messengers in Isolated Mouse Juxtaglomerular Cells

Abstract

In this study we have characterized the synthesis and secretion of renin in short-term cultures of isolated mouse renal juxtaglomerular (JG) cells. Our findings suggest that those cultures can be utilized to study the control of renin secretion and synthesis in parallel. With this experimental model, we have examined whether renin synthesis and secretion are concordantly regulated by second-messenger molecules such as cyclic nucleotides and protein kinase C. We found that 8-bromo-cyclic GMP (8-bromo-cGMP; 100 µ<i>M</i>) inhibited and forskolin (1 µM) and isoproterenol (10 µ<i>M</i>) enhanced basal renin secretion during a 20-hour incubation period. Stimulation of renin secretion by forskolin was not altered by 8-bromo-cGMP or 12-phorbol-myristate-13 acetate (PMA). Forskolin and isoproterenol also led to a stimulation of renin synthesis, which became apparent with a delay of several hours after the stimulation of renin secretion. 8-Bromo-cGMP and PMA did not alter basal renin synthesis. PMA but not 8-bromo-cGMP blunted the stimulation of renin synthesis in the presence of forskolin. Our findings suggest that a rise of cyclic AMP (cAMP) in JG cells is a positive signal for both the secretion and the synthesis of renin. cGMP is only inhibitory for renin secretion if cAMP levels are not elevated. Protein kinase C activation appears to be a potent inhibitory signal for cAMP-stimulated renin synthesis. Our findings, moreover, suggest that the second-messenger control of renin secretion and of renin synthesis are not tightly linked in renal JG cells.