POTENTIATING EFFECTS OF CALCIUM CHELATORS ON BASAL AND STIMULATED ALDOSTERONE PRODUCTION BY BOVINE ADRENAL GLOMERULOSA CELLS IN-VITRO

We previously reported the potentiation of basal aldosterone productio n by the addition of the calcium chelator ethyleneglycol-bis-(beta-ami noethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to an extracellular s olution of bovine adrenal glomerulosa cells in vitro. To assess whethe r the addition of the calcium chelators ethylenediamine-N,N,N',N'-tetr aacetic acid (EDTA) and EGTA can potentiate bas al and stimulated aldo sterone production, we compared the effect of EDTA with that of EGTA o n basal and the agonist (potassium; 8 mM, angiotensin II; 10 nM, ACTH; 10 nM)-stimulated aldosterone production by the cells in vitro. These two chelators lowered the extracellular ionized calcium ([Ca2+](i)) c oncentration in a similar manner. The levels of basal and the agonist- stimulated aldosterone production in the presence of EDTA (1 mM) and E GTA (1 mM) were significantly (P<0.01 or less) increased when compared with those in the absence of EDTA and EGTA, respectively. These resul ts show that the addition of EDTA and EGTA to an extracellular solutio n potentiates basal and the agonist-stimulated aldosterone production in vitro. Although an increase in basal aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) was completely inhibited by th e voltage-dependent calcium channel antagonist nifedipine (1 mu M) or the calmodulin antagonist pimozide (1 mu M), the potentiation of the a gonist-stimulated aldosterone production does not seem to be induced b y Ca2+/calmodulin-dependent nor cAMP-dependent systems. These findings suggest that calcium chelators such as EDTA and EGTA may possess acti vating effect on basal and stimulated aldosterone production in bovine adrenal glomerulosa cells.