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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The zones of the adrenal cortex contain distinct populations of cells which share a common developmental origin and steroidogenic template. In the rat, zona glomerulosa cells respond to angiotensin II (Ang II) with increased steroidogenesis while zona fasciculata/reticularis cells do not. We have examined Ang II-mediated signal transduction in homogeneous cellular sub-populations derived from either the zona glomerulosa (GLOM) or the zona fasciculata (FASC). In both of these sub-populations Ang II treatment significantly increased the levels of 3H-labelled inositol phosphates as well as the total mass of inositol 1,4,5-triphosphate. In contrast, the two cell types exhibited very different Ang II-mediated changes in free intracellular calcium ([Ca2+]i). Ang II (10 nM), induced [Ca2+]i increases of > 50 nM in 90% of individual GLOM cells (53/58), but in only 28% of FASC cells (11/39). These [Ca2+]i responses occurred after a transient Ang II stimulation ( < 1 min), in the presence of verapamil and in the absence of extracellular calcium, indicating an intracellular release. In small groups of 10-30 cells, stimulation with 1, 10 and 100 nM Ang II induced [Ca2+]i increases of 78, 178 and 215 nM respectively in GLOM cultures compared to only 35, 64, and 65 nM in FASC cultures. Thapsigargin treatment, which releases intracellular calcium in an inositol phosphate independent manner, elicited [Ca2+]i increases in both populations. Importantly, a calcium ionophore induced elevation of [Ca2+]i increased steroidogenesis in both cell types. These results suggest that an interruption of the signaling cascade at the level of intracellular calcium release contributes to the lack of a steroidogenic response to Ang II by the FASC cells. Therefore, in the rat adrenal cortex, divergent differentiation of related cell types may involve alterations within signal transduction pathways distal to initial receptor-mediated events (i.e. inositol phosphate production) and proximal to downstream effector events (i.e. steroidogenesis).
Mol Cell Endocrinol 1992 Nov
PMID:Divergent differentiation of rat adrenocortical cells is associated with an interruption of angiotensin II-mediated signal transduction. 130 86

Results of previous studies indicated that insulin at levels comparable to those in humans during hyperinsulinemia decreased ACTH-stimulated cortisol and androstenedione secretion by bovine adrenal fasciculata-reticularis cells in primary culture. In the present studies this inhibitory action was examined further by comparing the effects of insulin on ACTH-stimulated corticosteroid secretion with its effects on 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), forskolin- and [5val]angiotensin II (Ang II)-stimulated corticosteroid secretion. Effects on corticosteroid secretion were correlated with effects on cAMP accumulation and rates of cAMP production. Monolayers were incubated for 24 h in the absence or presence of each agonist alone or in combination with insulin. Insulin (1.7 x 10(-9) or 17.5 x 10(-9) M) caused about a 50% decrease in cortisol and androstenedione secretion in response to ACTH (10(-11) or 10(-8) M). Insulin also decreased ACTH-stimulated aldosterone secretion by cultured glomerulosa cells. Cpt-cAMP (10(-4) or 10(-3) M)-stimulated increases in cortisol and androstenedione secretion were inhibited by insulin, but to a lesser extent than those in response to ACTH. The inhibition of cpt-cAMP-stimulated steroid secretion was not related to increased degradation of the cyclic nucleotide. Increases in cortisol and androstenedione secretion caused by a submaximal concentration (10(-6) M) of forskolin were decreased 50-70% by insulin. In contrast, insulin failed to significantly affect cortisol or androstenedione secretion caused by a maximal concentration (10(-5) M) of forskolin. The secretory responses to Ang II (10(-8) M) were also unaffected by insulin. The effect of insulin to inhibit ACTH-stimulated steroid secretion was accompanied by a reduction in cAMP accumulation as well as an apparent inhibition of adenylate cyclase activation. These data indicate that the effect of insulin to attenuate ACTH-stimulated corticosteroid secretion results from both an inhibition of ACTH-stimulated adenylate cyclase activity and an antagonism of the intracellular actions of cAMP.
J Steroid Biochem Mol Biol 1992 Jan
PMID:Mechanisms of insulin inhibition of ACTH-stimulated steroid secretion by cultured bovine adrenocortical cells. 137 Sep 6

The stimulatory effects of angiotensin (Ang) I, Ang II, and Ang III on production of diacylglycerol (DAG), a second messenger, were examined in porcine pulmonary artery endothelial cells. Ang I, Ang II, and Ang III provoked rapid increases in [3H]glycerol labeling of DAG. The stimulatory effect on DAG production was maximal after 1 and 5 min. Pretreatment of cells with angiotensin-converting enzyme activity inhibitors prevented the stimulatory effect of Ang I on DAG production, indicating that Ang II but not Ang I is responsible for increased DAG production. The stimulatory effects of Ang II and Ang III on DAG production were concentration dependent and were maximal at a 10-nM concentration of both Ang II and Ang III. Data from further experiments revealed that the Ang II- and Ang III-elicited formation of DAG is derived from the coordinated hydrolysis of membrane phosphatidylinositol and phosphatidylcholine by phospholipase C- and phospholipase D-catalyzed pathways. The angiotensin analogue [Sar1 Ile8] Ang II, an Ang II receptor antagonist, blocked the hydrolysis of phosphatidylinositol and phosphatidylcholine and thus the increased production of DAG by Ang II and Ang III. These results indicate that Ang II- and Ang III-induced stimulation of DAG production in pulmonary artery endothelial cells involves multiple pathways of phospholipid hydrolysis and is mediated by angiotensin receptors.
Am J Respir Cell Mol Biol 1991 Oct
PMID:Angiotensin receptor-mediated stimulation of diacylglycerol production in pulmonary artery endothelial cells. 191 Aug 16

Angiotensin (Ang) II causes hypertrophy of rat aortic smooth muscle cells in culture and results in the rapid activation of c-fos. This study demonstrated that Ang II also activated c-jun and, in addition, could activate the AP-1 enhancer element. These data add support for a role of Ang II as an important mediator of vascular smooth muscle cell growth.
Mol Cell Biol 1990 Oct
PMID:Induction of the proto-oncogene c-jun by angiotensin II. 211 1

In vitro differentiation of murine neuroblastoma N1E-115 cells induced by low serum (0.5%) and dimethyl sulfoxide (1.5%) increased the uptake of 45Ca2+ as well as basal and forskolin-stimulated adenylate cyclase activity. Associated with these biochemical indices of differentiation was an increase in the density of binding sites for the angiotensin II (Ang II) receptor agonist 125I-[Sar1]-Ang II and the antagonist 125I-[Sar1,Ile8]-Ang II (125I-SARILE). This up-regulation was apparent within 24 hr and was maximal at 72 hr. Other manipulations that independently increased intracellular cAMP or Ca2+ levels produced a qualitatively similar up-regulation of Ang II receptors. In vitro differentiation did not diminish the specificity of these receptors for Ang-II related peptides. Sarcosine-substituted Ang II receptor antagonists such as [Sar1,Gly8]-Ang II, [Sar1,Thr8]-Ang II, or SARILE itself competed for 125I-SARILE in a monophasic fashion, whereas the competition displayed by the agonists Ang II, angiotensin III, and Crinia-Ang II for 125I-SARILE-labeled sites was biphasic, consisting of distinct high and low affinity components. Moreover, in vitro differentiation predominantly increased the density of high affinity sites for angiotensin III and Crinia-Ang II, but the lower affinity site for Ang II, and in all three cases the majority of this increased binding was insensitive to guanine nucleotides. Collectively, these results demonstrate that the expression of Ang II receptors on neuron-like cells is regulated by the biochemical events accompanying differentiation and suggest that the biphasic nature of the binding of some angiotensin agonists may be indicative of multiple receptor subtypes.
Mol Pharmacol 1990 Dec
PMID:Up-regulation of angiotensin II receptors by in vitro differentiation of murine N1E-115 neuroblastoma cells. 212 21

The evolution of our understanding of the actions of ANG II can be described in terms of 3 paradigms that also characterize the development of our knowledge of cardiovascular regulation. The first paradigm, organ physiology, described the variable performance of the heart in terms of length-dependent changes in myocardial contractile function (Starling's Law), and Ang II as a pressor factor that elevated blood pressure. With the shift to the second paradigm, cell biochemistry and biophysics, regulation of cardiac performance came to be explained by altered calcium fluxes and changing myocardial contractility, while the clinical effects of Ang II were understood in terms of changes in the calcium fluxes that control smooth muscle contraction. The third paradigm, gene expression (molecular biology), probably describes the most primitive--and complex--of these regulatory mechanisms. Altered gene expression in response to a variety of chemical and physical forces can explain several aspects of the long-term regulation of cardiac performance in terms of adaptative changes in the architecture and composition of a heterogeneous population of myocardial cells. This third paradigm also describes important effects of Ang II to increase protein synthesis and promote cell growth that appear able both to ameliorate and exacerbate human disease. It is, therefore, probably inappropriate to view Ang II mainly as a vasoconstrictor with secondary effects to induce cell hypertrophy. Instead, Ang II may have been derived from a primitive growth factor that, because it utilized Ca2+ to mediate its effects on gene expression, later in evolution acquired the ability to increase smooth muscle tone and myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1990 Jul
PMID:Angiotensin II: hemodynamic regulator or growth factor? 223 42

Neuronal cells from Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rat brains were established in culture to compare the expression of angiotensin II (Ang II) specific receptors and their regulation by norepinephrine (NE). Neurons from SH rat brains possess twice more Ang II specific receptors and expressed a proportional increase in Ang II stimulated [3H]-NE uptake compared with WKY neurons. NE caused a dose-dependent decrease in 125I-Ang II binding in WKY neurons, an effect not observed when neurons from SH rat brains were incubated with NE. These observations suggest that the lack of NE-induced downregulation of Ang II receptors in neuronal cultures is genetically regulated.
Mol Cell Biochem
PMID:Lack of alpha-1-adrenergic receptor-mediated downregulation of angiotensin II receptors in neuronal cultures from spontaneously hypertensive rat brain. 256 Jan 38

The stimulation of phosphoinositide metabolism by angiotensin II (Ang II) was studied in [3H]inositol-labelled bovine adrenal glomerulosa cells. After separation of the phosphoinositols by ion-exchange high-performance liquid chromatography, it was shown that the formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) followed distinct kinetics. The first compound to increase upon stimulation with 10(-7) M Ang II was Ins(1,4,5)P3, which reached a maximum (250% of basal level) within 10 s. At lower concentrations of Ang II, this response was slower. The formation of Ins(1,4,5)P3 depended upon the concentration of Ang II, with an EC50 of 2.4 +/- 1.5 X 10(-9) M Ang II. The potency of Ang II in stimulating the turnover of phosphoinositides and in increasing the biosynthesis of aldosterone was very similar, whereas the peptide was ten times more potent in its ability to mobilize Ca2+. Ang II was also able to stimulate the production of Ins(1,4,5)P3 in permeabilized glomerulosa cells. This effect was mimicked by a non-hydrolysable analog of GTP (GTP gamma S), suggesting that a GTP binding protein is involved in the mechanism coupling the Ang II membrane receptor to phospholipase C. These results strengthen the view that Ins(1,4,5)P3 plays a key role as second messenger in the steroidogenic response to Ang II in adrenal glomerulosa cells.
Mol Cell Endocrinol 1988 Jun
PMID:Inositol trisphosphate isomers in angiotensin II-stimulated adrenal glomerulosa cells. 326 Dec 66

In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.
Mol Endocrinol 1995 Aug
PMID:Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein. 747 91

In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists which activate phospholipase C stimulate tyrosine kinase activity in a calcium-dependent, protein kinase C (PKC)-independent manner. Since Ang II also produces a proliferative response in these cells, we investigated downstream signaling elements traditionally linked to growth control by tyrosine kinases. First, Ang II, like epidermal growth factor (EGF), stimulated AP-1 binding activity in a PKC-independent manner. Because increases in AP-1 can reflect induction of c-Jun and c-Fos, we examined the activity of the mitogen-activated protein (MAP) kinase family members Erk-1 and -2 and the c-Jun N-terminal kinase (JNK), which are known to influence c-Jun and c-Fos transcription. Ang II stimulated MAP kinase (MAPK) activity but only approximately 50% as effectively as EGF; again, these effects were independent of PKC. Ang II also produced a 50- to 200-fold activation of JNK in a PKC-independent manner. Unlike its smaller effect on MAPK, Ang II was approximately four- to sixfold more potent in activating JNK than EGF was. Although others had reported a lack of calcium ionophore-stimulated JNK activity in lymphocytes and several other cell lines, we examined the role of calcium in GN4 cells. The following results suggest that JNK activation in rat liver epithelial cells is at least partially Ca(2+) dependent: (i) norepinephrine and vasopressin hormones that increase inositol 1,4,5-triphosphate stimulated JNK; (ii) both thapsigargin, a compound that produces an intracellular Ca(2+) signal, and Ca(2+) ionophores stimulated a dramatic increase in JNK activity (up to 200-fold); (iii) extracellular Ca(2+) chelation with ethylene glycol tetraacetic acid (EGTA) inhibited JNK activation by ionophore and intracellular chelation with 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl-ester (BAPTA-AM) partially inhibited JNK activation by Ang II or thapsigargin; and (iv) JNK activation by Ang II was inhibited by pretreatment of cells with thapsigargin and EGTA, a procedure which depletes intracellular Ca(2+) stores. JNK activation following Ang II stimulation did not involve calmodulin; either W-7 nor calmidizolium, in concentrations sufficient to inhibit Ca(2+)/calmodulin-dependent kinase II, blocked JNK activation by Ang II. In contrast, genistein, in concentrations sufficient to inhibit Ca(2+)-dependent tyrosine phosphorylation, prevented Ang II and thapsigargin-induced JNK activation. In summary, in GN4 rat liver epithelial cells, Ang II stimulates JNK via a novel Ca(2+)-dependent pathway. The inhibition by genistein suggest that Ca(2+)-dependent tyrosine phosphorylation may modulate the JNK pathway in a cell type-specific manner, particularly in cells with a readily detectable Ca(2+)-regulated tyrosine kinase.
Mol Cell Biol 1995 Nov
PMID:Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal kinase. 756 68


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