Angiotensin II potentiates adrenocorticotrophic hormone-induced cAMP formation in bovine adrenal glomerulosa cells through a capacitative calcium influx

Abstract

Angiotensin II (AngII) plays a crucial role in the control of aldosterone biosynthesis in adrenal glomerulosa cells through the stimulation of two distinct Ca2+ entry pathways: (1) opening of voltage-operated calcium channels, and (2) activation of a capacitative Ca2+ entry that is dependent on calcium release from intracellular pools. Adrenocorticotrophic hormone (ACTH), on the other hand, a major hormonal regulator of steroidogenesis, induces an increase in intracellular cAMP through the activation of a G-protein-coupled adenylyl cyclase. Recent studies have demonstrated that the rise in cAMP induced by ACTH can be potentiated by AngII in bovine glomerulosa cells. The aim of the present study was to investigate the mechanism of AngII action on ACTH-induced cAMP production. In primary cultures of bovine glomerulosa cells, we found that AngII (100 nM), which had no effect by itself on cAMP production, significantly potentiated maximal ACTH-induced cAMP formation in the presence of extracellular calcium (1.2 mM). In contrast, in the absence of extracellular calcium, AngII did not affect ACTH-induced cAMP production. These results suggest that calcium entry into the cell plays an important role in the activation of the cyclase by AngII. The inhibition of voltage-operated calcium channels by nicardipine, a dihydropyridine calcium antagonist blocking both low-threshold (T-type) and high-threshold (L-type) Ca2+ channels, did not significantly affect the potentiating effect of AngII. Moreover, the cAMP response to ACTH was insensitive to activation of these Ca2+ channels induced by potassium ions and, even when cytosolic free-calcium concentration ([Ca2+]c) was kept elevated with the Ca2+ ionophore, ionomycin, no stimulation of adenylyl cyclase was observed at concentrations of [Ca2+]c up to 640 nM. In contrast, thapsigargin, an activator of capacitative Ca2+ influx, mimicked the potentiating effect of AngII on ACTH-induced cAMP formation. In agreement with the characteristics of cAMP modulation by Ca2+ in these cells, the presence of type III adenylyl cyclase was observed by immunodetection in bovine glomerulosa cell membranes. In conclusion, these data suggest a tight coupling between the capacitative Ca2+ influx induced upon stimulation by either AngII or thapsigargin and a calcium-sensitive isoform of adenylyl cyclase, probably type III, in bovine glomerulosa cells.

Characteristics of the Ca2+‐dependent inhibition of cyclic AMP accumulation by histamine and thapsigargin in human U373 MG astrocytoma cells

“…The marked reduction of the inhibitory action of thapsigargin in the absence of added Ca 2+ and in the presence of EGTA indicates that Ca 2+ released from intracellular stores plays only a minor role in inhibition of cyclic AMP accumulation, at most. This is consistent with the conclusion drawn from experiments on HEK 293 cells transfected with the type VI (Cooper et al, 1994) and type VIII adenylyl cyclase (Shuttleworth & Thompson, 1999), on native C6-2B glioma cells (Chiono et al, 1995;Fagan et al, 1998), on bovine adrenal glomerulosa cells (Burnay et al, 1998) and on mouse parotid acini (Watson et al, 1998) that it is Ca 2+ entry via capacitative entry channels which produces signi®cant modulation of cyclic AMP accumulation.…”

Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion

“…, was found in human (Cote et al, 2001), rat (Nishimoto et al, 2013) and bovine (Burnay et al, 1998) glomerulosa cells. On the contrary, a reduced cAMP formation was reported in angiotensin II -stimulated rat glomerulosa (Bell et al, 1981;Woodcock and Johnston, 1984) or bovine adrenocortical cells (Begeot et al, 1988;Marie and Jard, 1983 -inhibited isoforms (AC5 and AC6, (human: (Cote et al, 2001), rat: (Shen et al, 1997)) is a species (or cell) specific feature and may account for the different results obtained in different models.…”

“…Although ACTH and angiotensin II act synergistically on aldosterone secretion (Spät and Hunyady, 2004), several laboratories reported that angiotensin II reduces basal and ACTHinduced cAMP production (Bell et al, 1981;Marie and Jard, 1983;Woodcock and Johnston, 1984;Begeot et al, 1987) (but see (Baukal et al, 1994;Burnay et al, 1998)). This inhibition has been attributed to the activation of the inhibitory G-protein, G i (Enyedi et al, 1986;Hausdorff et al, 1987;Lu et al, 1996;Maturana et al, 1999;Rocco et al, 1990).…”

Janus Kinase 2 and Calcium Are Required for Angiotensin II-dependent Activation of Steroidogenic Acute Regulatory Protein Transcription in H295R Human Adrenocortical Cells

“…2A, ϩCa) (12). The transient rise in [Ca 2ϩ ] i has been attributed to the release of internal stores, while the sustained levels are a result of influx of extracellular calcium to fill these depleted membrane stores (1,4,42). The maximal [Ca 2ϩ ] i measured is referred to as peak calcium, while the sustained calcium level is reported as the calcium concentration 3-5 min after agonist treatment.…”