Control of renin secretion by Ca2+ and cyclic AMP through two parallel mechanisms.
The cellular mechanism of action of cyclic AMP (cAMP) mediating the beta-adrenergic stimulation of renin secretion was studied, with special reference to its interactions with the inhibitory pathway of renin secretion by Ca2+ calmodulin. Forskolin, a potent stimulator of adenyl cyclase that bypasses the hormone-receptor interactions, stimulated renin secretion in vitro from rabbit renal cortical slices in a concentration-dependent manner. Renin secretion stimulated by submaximal concentration of forskolin was partly or completely antagonized or blocked by raising intracellular Ca2+ concentration by incubating slices in a high-K+ depolarizing medium, but renin secretion stimulated by the maximal effective concentration of forskolin was not inhibited by Ca2+. In addition, the maximal effective concentration of forskolin (10(-5) M) increased renin secretion by a fixed amount independent of medium (by inference, intracellular) Ca2+ concentration in the range of 10(-8) to 10(-6) M in a high-K+ medium. Furthermore, the degree of stimulation of renin secretion by forskolin was greater with greater removal of the inhibitory effect of Ca2+ calmodulin pathway on renin secretion with use of potent calmodulin antagonists, suggesting that the stimulatory effect of cAMP on renin secretion may be maximal in the absence of the inhibitory influence of Ca2+. These results are consistent with the hypothesis that cAMP (by inference, the beta-adrenergic stimulus) stimulates renin secretion through a cellular mechanism independent of that through the Ca2+ -calmodulin pathway.
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009994:Osmolar Concentration; D011817:Rabbits; D012083:Renin / Q000378:metabolism*; D013268:Stimulation, Chemical
D002147:Calmodulin; D005576:Colforsin; D000242:Cyclic AMP; D012083:Renin; D002118:Calcium