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

1998 ◽  
Vol 330 (1) ◽  
pp. 21-27 ◽  
Author(s):  
M. Muriel BURNAY ◽  
B. Michel VALLOTTON ◽  
M. Alessandro CAPPONI ◽  
F. Michel ROSSIER
Keyword(s):  
Angiotensin Ii ◽  
Calcium Channels ◽  
Adenylyl Cyclase ◽  
Adrenocorticotrophic Hormone ◽  
Camp Production ◽  
Glomerulosa Cells ◽  
Camp Formation ◽  
Voltage Operated Calcium Channels ◽  
Ca2 Channels ◽  
Stimulation Of

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.

scholarly journals Inositol phosphate release and steroidogenesis in rat adrenal glomerulosa cells. Comparison of the effects of endothelin, angiotensin II and vasopressin

1990 ◽  
Vol 271 (3) ◽  
pp. 791-796 ◽  
Author(s):  
E A Woodcock ◽  
P J Little ◽  
J K Tanner
Keyword(s):  
Angiotensin Ii ◽  
Metabolic Pathways ◽  
Inositol Phosphate ◽  
The Other ◽  
Relative Importance ◽  
Phosphate Release ◽  
Phosphatidylinositol Turnover ◽  
Transient Rise ◽  
Glomerulosa Cells ◽  
Stimulation Of

Endothelin has steroidogenic activity in adrenal glomerulosa cells, as do two other vasoconstrictor peptides, angiotensin II and vasopressin. The steroidogenic activities of angiotensin II and vasopressin are probably mediated via the phosphatidylinositol-turnover pathway and associated changes in cytosolic Ca2+ concentration. Endothelin caused a steroidogenic response, which was small compared with that to angiotensin II and quantitatively similar to the vasopressin response. Cytosolic free Ca2+ responses were similarly higher to angiotensin II than to either of the other two peptides. However, total inositol phosphate responses to endothelin and angiotensin II were similar when these were measured over 20 min, and were quantitatively greater than the vasopressin response. A detailed study has been made of the phosphatidylinositol-turnover response to endothelin in comparison with responses to angiotensin II and vasopressin. Each of the three peptides produced a rapid and transient rise in Ins(1,4,5)P3 (max. 5-15 s), followed by a slow sustained rise. Ins(1,4,5)P3 was metabolized by both dephosphorylation and phosphorylation pathways, but the relative importance of the two metabolic pathways was different under stimulation by each of the three peptides. These findings show that adrenal glomerulosa cells can distinguish between the stimulation of phosphatidylinositol turnover by three different effectors. These differences in the pathway may be associated with the observed different steroidogenic and Ca2+ responses to the three peptides.

Capacitative Ca2+ influx in adrenal glomerulosa cells: possible role in angiotensin II response

1994 ◽  
Vol 267 (5) ◽  
pp. C1246-C1252 ◽  
Author(s):  
T. Rohacs ◽  
A. Bago ◽  
F. Deak ◽  
L. Hunyady ◽  
A. Spat
Keyword(s):  
Angiotensin Ii ◽  
Free Medium ◽  
Normal Medium ◽  
Fura 2 ◽  
Initial Rise ◽  
Glomerulosa Cells ◽  
High Concentrations ◽  
Ca2 Channels

We examined the effect of the depletion of intracellular Ca2+ stores on Ca2+ influx in rat glomerulosa cells. Depletion of intracellular Ca2+ stores was achieved by inhibiting sarco/endoplasmic reticulumtype Ca(2+)-ATPase with thapsigargin or 2,5,di-(t-butyl)-1,4-benzohydroquinone (t-BHQ). Both inhibitors induced a sustained rise in cytoplasmic Ca2+ concentration. The initial rise was observed also in Ca(2+)-free medium, while the sustained phase disappeared, indicating that the latter requires Ca2+ influx. In Ca(2+)-free medium, the readdition of Ca2+ induced a steeper and higher rise in intracellular Ca2+ concentration in thapsigargin-treated cells than in controls, supporting the role of Ca2+ influx. In normal medium, the addition of Cd2+ (80 microM) evoked an immediate inhibition of the sustained phase of thapsigargin response. The response to thapsigargin was insensitive to nifedipine. Thapsigargin failed to enhance Mn2+ quenching of fura 2. Our results provide evidence for the existence of capacitative Ca2+ influx in rat glomerulosa cells and indicate that dihydropyridine-sensitive Ca2+ channels do not participate in capacitative Ca2+ entry. High concentrations of thapsigargin and t-BHQ, similar to the reported effects of angiotensin II and vasopressin, inhibited K(+)-induced Ca2+ signals. These effects appear, however, to be independent of the depletion of internal Ca2+ stores.

Mechanism of action of γ-aminobutyric acid on frog melanotrophs

1995 ◽  
Vol 14 (1) ◽  
pp. 1-12 ◽  
Author(s):  
L Desrues ◽  
H Vaudry ◽  
M Lamacz ◽  
M C Tonon
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Inhibitory Effect ◽  
Aminobutyric Acid ◽  
Calcium Stores ◽  
Camp Production ◽  
Biphasic Effect ◽  
Camp Levels ◽  
Camp Formation ◽  
Stimulation Of

ABSTRACT We have previously demonstrated that γ-aminobutyric acid (GABA) is a potent regulator of secretory and electrical activity in melanotrophs of the frog pituitary. The aim of the present study was to investigate the intracellular events which mediate the response of melanotrophs to GABA. We first observed that GABA (1–100 μm inhibited both basal and forskolin-stimulated cyclic AMP (cAMP) formation. The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 μm) and totally abolished by a 4-h pretreatment with pertussis toxin (01 μg/ml). In contrast, the specific GABAA agonist 3-aminopropane sulphonic acid (3APS) did not affect cAMP production. Both GABA and 3APS (100 μm each) induced a biphasic effect on α-MSH release from perifused frog neurointermediate lobes, i.e. a transient stimulation followed by an inhibition of α-MSH secretion. Administration of forskolin (10 μm) prolonged the stimulatory phase and attenuated the inhibitory phase evoked by GABA and 3APS, indicating that cAMP modulates the response of melanotrophs to GABAA agonists. Ejection of 3APS (1 μm) in the vicinity of cultured melanotrophs caused a massive increase in intracellular calcium concentration ([Ca2+]i). The stimulatory effect of 3APS on [Ca2+]i was abolished when the cells were incubated in a chloride-free medium. The formation of inositol trisphosphate was not affected by 3APS, suggesting that the increase in [Ca2+]i cannot be ascribed to mobilization of intracellular calcium stores. ω-Conotoxin did not alter the secretory response of frog neurointermediate lobes to 3APS, while nifedipine blocked the stimulation of α-MSH secretion induced by 3APS. In conclusion, the present data indicate that, in frog pituitary melanotrophs, (i) the stimulatory phase evoked by GABAA agonists can be accounted for by an influx of calcium through L-type calcium channels, (ii) the inhibitory effect evoked by GABAB agonists can be ascribed to inhibition of adenylate cyclase activity and (iii) cAMP attenuates the inhibitory phase evoked by GABAA agonists. Taken together, these data suggest that activation of GABAB receptors may modulate GABAA receptor function.

scholarly journals G protein-regulated endocytic trafficking of adenylyl cyclase type 9

2020 ◽  
Author(s):  
André M. Lazar ◽  
Roshanak Irannejad ◽  
Tanya A. Baldwin ◽  
Aparna A. Sundaram ◽  
J. Silvio Gutkind ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Subcellular Location ◽  
Endocytic Pathway ◽  
Heterotrimeric G Proteins ◽  
Camp Production ◽  
Stimulation Of

SummaryGPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network, but little is known about how relevant G protein effectors are localized. Here we report dynamic trafficking of adenylyl cyclase type 9 (AC9) from the plasma membrane to endosomes, while adenylyl cyclase type 1 (AC1) remains in the plasma membrane, and stimulation of AC9 trafficking by ligand-induced activation of Gs-coupled GPCRs or Gs. AC9 transits a similar dynamin-dependent early endocytic pathway as activated GPCRs but, in contrast to GPCR trafficking which is regulated by β-arrestin but not Gs, AC9 trafficking is regulated by Gs but not β-arrestin. We also show that AC9, but not AC1, contributes to cAMP production from endosomes. These results reveal dynamic and isoform-specific trafficking of adenylyl cyclase in the endocytic network, and a discrete role of a heterotrimeric G protein in controlling subcellular location of a relevant effector.

Sustained stimulation of aldosterone production by angiotensin II is potentiated by nickel

1990 ◽  
Vol 258 (4) ◽  
pp. E555-E561 ◽  
Author(s):  
A. Spat ◽  
I. Balla ◽  
T. Balla ◽  
P. Enyedi ◽  
G. Hajnoczky ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Adrenocorticotropic Hormone ◽  
Inositol Phosphates ◽  
Phospholipid Metabolism ◽  
Suitable Tool ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Induced Changes ◽  
Stimulation Of

Angiotensin-induced aldosterone production by superfused adrenal glomerulosa cells was potentiated by Ni2+ (0.1 mM), added either at the onset of stimulation with angiotensin II or 1 h later. Nickel did not influence the effect of adrenocorticotropic hormone or potassium on aldosterone production. Nickel failed to modify angiotensin-induced changes in phospholipid metabolism or the formation of inositol phosphates and slightly reduced the enhancement of 45Ca influx. Uptake of Ni2+ into glomerulosa cells was increased by depolarization in a dihydropyridine-insensitive manner. Because nickel selectively potentiates the sustained phase of the response to a calcium-mobilizing hormone, it may serve as a suitable tool in elucidating the signal transduction process during the sustained phase of stimulation.

Angiotensin II and potassium activate different calcium entry mechanisms in rat adrenal glomerulosa cells

1989 ◽  
Vol 122 (1) ◽  
pp. 361-370 ◽  
Author(s):  
A. Spät ◽  
I. Balla ◽  
T. Balla ◽  
E. J. Cragoe ◽  
Gy. Hajnóczky ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Angiotensin Ii ◽  
Calcium Channels ◽  
Small Reduction ◽  
Nickel Ions ◽  
Ca Uptake ◽  
Voltage Dependent ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Isolated Rat

ABSTRACT Initial 45Ca uptake was measured in isolated rat glomerulosa cells. A small reduction in membrane potential produced by increasing the K+ concentration from 2 to 3·6 mmol/l stimulated 45Ca uptake by about 35%, while a bigger depolarization induced by 18·5 mmol K+/l increased the uptake by about 100%. Since Ca2+ influx was already activated at a calculated membrane potential below −70 mV, and was found to be sensitive to the dihydropyridine antagonist nifedipine (1 μmol/l), but insensitive to nickel ions (100 μmol/l), it does not meet the criteria established for T- or L-type voltage-dependent Ca2+ channels. Exposure of glomerulosa cells to angiotensin II (AII) for 10 min also enhanced the rate of 45Ca influx. The effect of AII was not sensitive to 1 μmol nifedipine/l, but was strongly inhibited by 5-(N-4-chlorobenzyl)-N-(2′,4′-dimethyl)benzamil (CBDMB, 30 μmol/l), an inhibitor of the Na+/Ca2+ antiporter. These observations suggest that during the sustained phase of stimulation with AII, a CBDMB-sensitive mechanism, rather than dihydropyridine-sensitive calcium channels, is involved in Ca2+ uptake in rat glomerulosa cells. The bulk Ca2+ influx did not correlate with aldosterone production; however, the maintained activity of different Ca2+ entry mechanisms seems to be essential for AII-induced aldosterone production. Journal of Endocrinology (1989) 122, 361–370

Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production

1993 ◽  
Vol 265 (2) ◽  
pp. E179-E183 ◽  
Author(s):  
E. N. Cozza ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Direct Stimulation ◽  
Potentiation Effect ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Pkc Inhibitors ◽  
Stimulation Of

Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC.

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