Enhancement of beta-adrenergic cAMP-signaling by the mineralocorticoid receptor

We examined the modulation of adrenergic cell signaling by the human mineralocorticoid receptor (hMR) in renal cell lines (RC.SV3) stably transfected with full-length (M cells) or truncated hMR. Isoproterenol time-dependently increased intracellular cAMP formation, which was up to six-fold higher in M cells than in parental RC.SV3 cells. Incubation of cells with aldosterone or spironolactone for 24h neither changed the basal nor the isoproterenol-stimulated cAMP level in both cell lines, while inhibitor studies revealed that those effects are mediated by the beta(2)-adrenergic receptor. Expression of stimulatory G protein alpha was increased and that of G protein receptor coupled kinase 3 (GRK3) was reduced by hMR. Deletion studies of cells stably transfected with truncated hMR indicated that the N-terminal and the DNA binding domains of hMR are essential for enhancement of the catecholamine signal transduction pathway. In conclusion, our findings suggest a novel interplay between cAMP and MR signaling pathways.