Second messengers involved in the control of renin secretion in cultured human nephroblastoma cells

We aimed to study the intracellular signaling mechanisms involved in the stimulation and suppression of renin secretion from human nephroblastoma cells. Isoproterenol and forskolin increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration and stimulated renin secretion as did the addition of dibutyryl-cAMP. Atrial natriuretic peptide (ANP) suppressed basal renin secretion and increased the concentration of extracellular guanosine 3',5'-cyclic monophosphate (cGMP). When ANP was added in the presence of isoproterenol or forskolin, the increase in cGMP was reduced. ANP attenuated the cAMP response to isoproterenol but not forskolin. Nephroblastoma cell membranes contained the guanosine-binding proteins Gs and Gi2, and the isoforms were similar to those in vascular smooth muscle. A functional role for Gi was indicated because the ANP-induced suppression of basal renin secretion was blocked by pertussis toxin. We conclude that cAMP stimulates and cGMP suppresses basal renin secretion, but neither fully accounts for the suppression of stimulated renin secretion by ANP.