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 production by the addition of the calcium chelator ethyleneglycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to an extracellular solution of bovine adrenal glomerulosa cells in vitro. To assess whether the addition of the calcium chelators ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and EGTA can potentiate basal and stimulated aldosterone production, we compared the effect of EDTA with that of EGTA on 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+]o) concentration in a similar manner. The levels of basal and the agonist-stimulated aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) were significantly (P < 0.01 or less) increased when compared with those in the absence of EDTA and EGTA, respectively. These results show that the addition of EDTA and EGTA to an extracellular solution 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 the voltage-dependent calcium channel antagonist nifedipine (1 microM) or the calmodulin antagonist pimozide (1 microM), the potentiation of the agonist-stimulated aldosterone production does not seem to be induced by CA2+/calmodulin-dependent nor cAMP-dependent systems. These findings suggest that calcium chelators such as EDTA and EGTA may possess activating effect on basal and stimulated aldosterone production in bovine adrenal glomerulosa cells.
Kigoshi
T
T
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Okamoto
H
H
Ishii
T
T
Ito
T
T
Hotta
F
F
Kitazawa
M
M
Nishizawa
M
M
Nakano
S
S
Morimoto
S
S
Uchida
K
K
D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002469:Cell Separation; D002614:Chelating Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004492:Edetic Acid / Q000378:metabolism / Q000494:pharmacology; D004533:Egtazic Acid / Q000378:metabolism / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D002614:Chelating Agents; D000450:Aldosterone; D004533:Egtazic Acid; D004492:Edetic Acid