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Membrane permeability to K+ and the control of aldosterone synthesis: effects of valinomycin and cromakalim in bovine adrenocortical cells
in Journal of Molecular EndocrinologyABSTRACT
Stimulation of aldosterone synthesis by angiotensin II (AII) is associated with depolarization of the cell membrane. Since the potential difference of adrenocortical cells is dependent on membrane permeability to potassium ions, the effects of agents which hyperpolarize the cell (by increasing permeability to K+) on the control of aldosterone synthesis were investigated further. Basal and AII-stimulated aldosterone synthesis was increased by 20–70% in cells incubated with 1 or 10 nm of the potassium ionophore valinomycin; higher concentrations markedly inhibited AII-stimulated synthesis. Cromakalim, a potential antihypertensive drug which facilitates the opening of K+ channels in smooth muscle cells, stimulated basal aldosterone synthesis at 2 μm but had no effect at 40 μm. AII-stimulated aldosterone synthesis was not affected by cromakalim except at 40 μm, which was inhibitory. The inhibitory effects of cromakalim, unlike those of valinomycin, were not reversible. Aldosterone synthesis from added hydroxycholesterol and pregnenolone (but not from deoxycorticosterone and corticosterone) was significantly inhibited by 40 μm cromakalim.
Potassium efflux from cells preloaded with 43K was unaffected by low concentrations of valinomycin, but was markedly increased by concentrations which inhibited AII-stimulated aldosterone production. Small decreases and increases in 43K efflux, caused by 1 and 40 μm cromakalim respectively, corresponded with increases and decreases in basal aldosterone production; cromakalim did not affect 43K efflux from AII-stimulated cells.
We suggest that increasing adrenocortical cell membrane permeability to K+ reduces steroidogenesis, but that valinomycin and cromakalim have other actions which complicate the relationship between 43K efflux and aldosterone production. Cromakalim appears to inhibit 21-hydroxylase activity in the biosynthetic pathway and may also affect 3β-hydroxysteroid dehydrogenase activity.
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Online ISSN: 1479-6813
Print ISSN: 0952-5041
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