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ABSTRACT: Angiotensin II enhances phosphatidylinositol turnover in isolated adrenal glomerulosa cells. In the present experiments we examined whether this effect required the presence of extracellular Ca2+. It was found that neither the stimulation of phosphatidylinositol breakdown nor the stimulation of incorporation of [32P]phosphate into phosphatidic acid and phosphatidylinositol required the presence of extracellular Ca2+. These observations suggest that the enhancement of phosphatidylinositol turnover may precede, but does not depend on, angiotensin-induced Ca2+ influx.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism.
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ABSTRACT: The effect of angiotensin II on arachidonate metabolism was examined in rat adrenal glomerulosa cells. Incorporation of both [3H]arachidonate and [32P]phosphate into phosphatidylinositol (PI) were significantly stimulated by angiotensin II. These effects were abolished by lithium, a cation, which was found suitable to prevent increased synthesis of PI in our previous study (T. Balla et al., FEBS Letters171, 179, 1984). On the other hand, the phospholipase A2 inhibitor mepacrine failed to inhibit the increased labelling of PI. These observations suggest that the increased 3H labelling of PI occurs via CDP-diacylglycerol, and not via enhanced deacylation-reacylation cycle. The validity of this assumption was further supported, since angiotensin II failed to stimulate the formation of lyso-PI, as examined by both [32P]phosphate incorporation and pulse-chase techniques.Angiotensin II decreased the incorporation of [3H]arachidonate into phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Considering that we did not find arachidonate release either from phospholipids or from other possible arachidonate sources this decrease may not be due to dilution of the tracer. Thus we assume that angiotensin II may induce a shift in phospholipid synthesis from PC and PE to phosphoinositides.These observations indicate that the enhanced hydrolysis and synthesis of PI in response to angiotensin II is not associated with increased phospholipase A2 activity in adrenal glomerulosa cells.
Biochemical Pharmacology.
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ABSTRACT: The purpose of the present experiments was to compare the effects on phosphatidylinositol metabolism of agents stimulating aldosterone secretion. Glomerulosa cells, isolated from rat adrenals, were incubated in the presence of one of the following stimuli: angiotensin II, elevated potassium concentration, corticotropin, dibutyryl cyclic AMP and prostaglandin E2. Of all these substances, only angiotensin II stimulated the incorporation of [32Piphosphate into phosphatidylinositol. The effect was already detected 2.5 min and was still maintained 60 min after the onset of stimulation. A slight enhancement of the incorporation into other phospholipids was observed in the first minutes of stimulation. Cycloheximide abolished the effect of angiotensin II on aldosterone production, but not on phosphatidylinositol synthesis. In cells prelabelled with [32P]phosphate, radioactivity in phosphatidylinositol relative to that in other phospholipids decreased in response to angiotensin II within 5 min. This indicates that angiotensin II induces a specific breakdown of phosphatidylinositol. Corticotropin failed to enhance the incorporation of [32P]phosphate into phosphatidylinositol and other phospholipids in isolated fasciculate-reticularis cells. The results suggests that although both angiotensin II and potassium are presumed to act through changes in calcium metabolism, angiotensin alone generates the calcium signal by increased phosphatidylinositol turnover.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism.
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ABSTRACT: The effects of verapamil and trifluoperazine were examined on isolated rat adrenal glomerulosa cells so as to assess the role of calcium ion influx and calmodulin in the function of this cell population. Verapamil (10−5 and 10−4moles/1) slightly reduced the basal production rate of aldosterone and strongly inhibited the response to angiotensin II, potassium ions, corticotrophin (ACTH) and dibutyryl cyclic AMP (db-cAMP). The concentration of verapamil required to reduce the response to these agonists by 50% varied between 2 and 6 μmoles/1. Trifluoperazine (30 μmoles/1) slightly increased the basal production rate of aldosterone. The response to angiotensin and potassium was variably antagonized by 3 μmoles/1 trifluoperazine and completely inhibited by the drug at 30 μmoles/1. The antagonist at a concentration of 3 μmoles/1 exerted either a facilitatory or inhibitory effect on the response to ACTH and db-cAMP, depending on the concentration of the agonist. Trifluoperazine at a concentration of 30 μmoles/1 reduced the response to both agonists to a level which was 2–3 fold higher than that observed in appropriate control samples. The present results indicate that (1) calcium influx is an essential event in the aldosterone stimulating action of angiotensin II, potassium ions, ACTH and cyclic AMP; (2) stimulation by angiotensin II and potassium ions are completely dependent on calmodulin; (3) stimulation by ACTH and cyclic AMP is mediated by calmodulin-dependent and independent mechanisms.
Biochemical Pharmacology.
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ABSTRACT: Angiotensin II stimulates rapid formation of inositol-1,4,5-triphosphate (Ins-1,4,5-P3) in bovine adrenal glomerulosa cells. In addition to being rapidly metabolized to lower inositol phosphates, Ins-1,4,5-P3 is converted to Ins-1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4) and Ins-1,3,4-P3 which is in turn phosphorylated to a further Ins-P4 isomer, namely Ins-1,3,4,6-P4. In bovine adrenocortical cytosol [3H]Ins-1,3,4,5-P4 and [3H]Ins-1,3,4-P3 were converted to Ins-1,3,4,6-P4 and inositol pentakisphosphate (Ins-P5) in a metabolic sequence suggesting that unlike Ins-1,3,4,5-P4, Ins-1,3,4,6-P4 is a direct precursor of Ins-P5. Consistent with this assumption, [3H]Ins-1,3,4,6-P4 was converted to Ins-P5 in electropermeabilized adrenal glomerulosa cells. These findings demonstrate that Ins-1,3,4,6-P4 is an intermediate link between InsP3 metabolism and the higher inositol phosphates detected in several tissues.
Biochemical and Biophysical Research Communications.
