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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we have investigated the effect of angiotensin-II (A-II) on cortisol production and 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha)) expression in primary cultures of ovine adrenocortical cells and the A-II receptor subtypes that mediate these responses. While A-II alone had no stimulatory effect on cortisol secretion, it inhibited the cortisol response to ACTH (10(-8) M) in a dose-dependent manner (Ki, less than 0.1 nM; maximum inhibition, 60-80%). While prolonged treatment with ACTH (10(-8) M) increased the expression of P450(17 alpha), cotreatment with A-II (10(-8) M) also inhibited ACTH-stimulated expression, as determined by changes in mRNA, immunoreactive P450(17 alpha), and 17 alpha-hydroxylase activity. A study of the effects of the AT1 and AT2 receptor antagonists, DuP 753 and PD 123319, on binding of [125I]A-II to ovine adrenocortical cells showed that the A-II receptor population was predominantly of the AT1 subtype. The effects of A-II on inhibition of cortisol secretion in response to ACTH and the activation of phosphoinositidase-C in response to A-II alone were both fully antagonized by DuP 753, but not by PD 123319. Furthermore, the inhibitory effects of A-II on expression of P450(17 alpha), as measured at the levels of mRNA, immunoreactive protein, and enzyme activity, were reversed by DuP 753 (10(-5) M), but not PD 123319 (10(-5) M). We conclude that A-II has a potentially important role in the control of cortisol secretion and long term maintenance of P450(17 alpha) expression in the ovine adrenal cortex, and that the effects of A-II on both cortisol secretion and P450(17 alpha) expression are mediated through the AT1 receptor, which is coupled to phosphoinositidase-C.
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PMID:Angiotensin-II acts via the type 1 receptor to inhibit 17 alpha-hydroxylase cytochrome P450 expression in ovine adrenocortical cells. 131 75

Mesangial cells possess a variety of receptors for hormones and autacoids. They are also equipped with ectoenzymes whose function may be to control the availability of autacoids and hormones at their receptor sites. Several examples are considered. Receptors for angiotensin II (AII) are present both on murine and human mesangial cells. One single group of receptors has been demonstrated in each of these preparations. Mesangial cell AII receptors are linked to phospholipase C via a G protein. They belong to the AT1 subtype because (125I)AII is displaced from its binding sites preferentially by AT1 antagonists such as DUP 753 and EXP 3,174, whereas AT2 antagonists are much less potent. AT1 antagonists suppress the biological effects of AII in mesangial cells, including the stimulation of intracellular calcium concentration and the increase of prostaglandin synthesis and of (3H)leucine incorporation. Mesangial cells also have receptors for atrial natriuretic factor, but the distribution between B receptors with guanylate cyclase activity and clearance (C) receptors varies with the species. Both types are present in murine mesangial cells, whereas only C receptors are found in human mesangial cells. In contrast, human epithelial cells possess both B and C receptors. Ecto-5'-nucleotidase activity results in the production of adenosine, which acts on mesangial cells through A1 and A2 receptors. This enzyme is markedly induced in rat mesangial cells by interleukin-1, whose effect is mediated in part by prostaglandin E2 and cAMP. Various other cAMP-stimulating agents also induce 5'-nucleotidase expression in rat mesangial cells. Ectopeptidases are present in all glomerular cell types but essentially in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell surface receptors and ectoenzymes in mesangial cells. 131 10

In search of the functional role of the newly found angiotensin II (Ang II) binding site which is expressed in differentiated Neuro-2A cells, we found that Ang II causes a marked stimulation of cGMP formation dose-dependently. The stimulation was blocked by the nonselective Ang II receptor antagonist [Sar1,Ile8]Ang II but not by the AT1 antagonist DuP 753 or the AT2 antagonist PD 123319. These results suggest that Ang II increased cGMP level via a new Ang II receptor subtype in differentiated Neuro-2A cells.
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PMID:A newly found angiotensin II receptor subtype mediates cyclic GMP formation in differentiated Neuro-2A cells. 132 79

The binding sites and biochemical effects of angiotensin (A) II were investigated in rat pheochromocytoma (PC12W) cells. Sarcosine1, [125I]-tyrosine4, isoleucine8-AII ([125I]-SI-AII) bound to a saturable population of sites on membranes with an equilibrium dissociation constant (Kd) of 0.4 nM and a binding site maximum of 254 fmol/mg protein. Competitive displacement of [125I]-SI-AII by agonists and antagonists elucidated a rank order of potency of AIII greater than or equal to AII greater than PD 123177 greater than AI greater than [des-Phe]AII [AII(1-7)] much greater than DuP 753. The stable guanine nucleotide analog 5'-guanylyl imidodiphosphate did not alter the binding affinity or slope of the inhibition curves for AI, AII, AIII, or AII(1-7). Treatment of PC12W cells with AII or AIII did not affect the free intracellular calcium concentration, phosphoinositide metabolism, arachidonate release, cyclic GMP, or cyclic AMP concentrations. [125I]-AII binding sites remained on the cell surface and were not internalized after 2 h at 37 degrees C. Angiotensin II did not stimulate tyrosine, serine, or threonine phosphorylation. Northern analysis of PC12W mRNA with an AT1 receptor gene probe failed to produce an RNA:DNA hybrid at low stringency. These data indicate that PC12W cells express a homogeneous population of AT2 binding sites which differ significantly from AT1 receptors in signal transduction and molecular structure. AT2 sites may act via potentially novel, biochemical pathways or, alternatively, be vestigial receptors.
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PMID:Molecular characterization of angiotensin II type II receptors in rat pheochromocytoma cells. 132 3

Angiotensin-II (A-II) receptor subtypes and their potential coupling mechanisms were investigated in bovine adrenal fasciculata cells (BAC) in culture, by the use of selective antagonists for AT1 (DUP 753 or Losartan) and AT2 (PD 123177 and CGP 42112A) sites. Competition for [125I]A-II specific binding with AT1 or AT2 selective ligands produced a biphasic displacement curve, suggesting two distinct A-II binding sites. In the presence of PD 123177 (10(-5) M), a concentration at which most of the AT2 sites were saturated, DUP 753 displaced [125I]A-II specific binding in a monophasic manner with an IC50 of 6.2 +/- 1.4 x 10(-7) M. In the presence of DUP 753 (10(-5) M), the displacement produced by CGP 42112A and PD 123177 was also monophasic, with IC50s of 8 +/- 3 x 10(-10) and 4.6 +/- 2.1 x 10(-7) M, respectively. The reducing agent dithio-1,4-erythritol inhibited the binding of [125I]A-II to AT1 (DUP 753 sensitive) sites, but increased its binding to AT2 sites 2-fold. The IC50 values for these two effects were about 0.5 and 3 mM, respectively. The biological effects of A-II in BAC, phosphoinositide hydrolysis and cortisol production, were inhibited in a dose-dependent manner by DUP 753, but not by AT2 antagonists. Similarly, the potentiating action of A-II on corticotropin-induced cAMP production was blocked by DUP 753, but not by AT2 antagonists. These data indicate that BAC contain both receptor subtypes, but that all the known effects of A-II in BAC were induced via the AT1 receptor subtype.
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PMID:Characterization and coupling of angiotensin-II receptor subtypes in cultured bovine adrenal fasciculata cells. 132 66

Quantitative autoradiography was used to determine the subtype of ANG receptors in the red pulp of the rat spleen. The AT1 antagonist DuP 753 competed for ANG binding with high affinity; binding was abolished by dithiothreitol. The AT2 competitor CGP 42112 A showed lower affinity, and the AT2 competitor PD 123177 did not affect binding at 10(-5) M. These data indicated the presence of only AT1 receptors. AT1 receptor number was similar in immature (2 weeks old) and adult (8 weeks old) rats. Binding was sensitive to guanine nucleotides, suggesting an association with G-proteins. Angiotensin II, at a dose of 10(-7) M, stimulated inositol phosphate formation 33% over control values in spleen from 8-week-old rats. This effect was significantly blocked by 10(-5) M DuP 753. We suggest a possible role of AT1 receptors in the regulation of splenic volume, blood flow, and lymphocyte function.
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PMID:Characterization of angiotensin II receptor subtypes in the rat spleen. 132 44

Angiotensin II is a vasoactive peptide and may act as a growth factor in vascular smooth muscle cells. Experimental injury of the rat aorta causes rapid migration of medial smooth muscle cells and their proliferation resulting in the formation of neointima. We have examined, using quantitative autoradiography, the expression of angiotensin II receptor subtypes AT1 and AT2, and angiotensin-converting enzyme, in the neointima formed in the rat thoracic aorta 15 d after balloon-catheter injury. In contrast to the normal aortic wall, which contained both AT1 and AT2 receptors (80% and 20%, respectively), neointimal cells expressed almost exclusively angiotensin II AT1 receptors. The apparent number of these receptors was fourfold higher in the neointima compared to that in the normal aortic wall. The affinities of the neointimal receptors to angiotensin II or to the AT1 receptor antagonist, losartan, were not different from those in the normal aortic wall. Angiotensin-converting enzyme binding in the neointima was not different from that in the media of the uninjured aorta. Our data suggest that angiotensin II AT1 receptors may have a significant role in injury-induced vascular smooth muscle proliferation and migration.
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PMID:Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta. 133 Nov 71

On the basis of biochemical and autoradiographic studies it has been shown that the inferior olivary nucleus (ION) contains predominantly angiotensin II (Ang II) receptors of the subtype 2 (AT2). In the present investigation we used microiontophoretic techniques to test the effect of Ang II on the spontaneous firing rate of rat neurones in the ION in vivo. Ang II excited the majority of histologically identified ION neurones. Furthermore, the antagonism of this angiotensin-induced excitation by selective angiotensin receptor blockers of subtype 1 and 2 (AT1 and AT2) was examined. The excitation could be blocked by low doses of the AT2-antagonists PD 123177 and CGP 42112A, whereas the AT1-antagonist DuP 753 was ineffective even at high doses. On a few occasions, however, ejection of the AT1-antagonist resulted in a potentiation of angiotensin-induced excitation. The results suggest that Ang II has an excitatory effect on a considerable number of ION neurones and that this effect is mediated by AT2-receptors.
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PMID:Effects of angiotensin II and its selective antagonists on inferior olivary neurones. 133 23

Radioligand binding studies were undertaken to establish the expression of angiotensin II (AII) receptors on the human hepatoma cell line, PLC-PRF-5. Cell membranes were shown to express a large number of AII receptors with high and low affinity binding sites having Bmax values of 1269 +/- 365 and 4190 +/- 1055 fmol/mg protein and affinities (Kd) of 2.0 +/- 0.3 nM and 8.7 +/- 0.4 nM, respectively. In intact cells a single class of AII binding site was seen with an affinity (Kd) of 6.7 +/- 1 nM and a Bmax value of 315 +/- 32 fmol/mg. In both membranes and intact cells AII, AIII and the selective angiotensin AT1 receptor antagonist, DuP 753, all had a high affinity for the receptor (Ki values in the nanomolar range), but the selective angiotensin AT2 ligands, PD 123177 and p-aminophenylalanine6 AII, had low affinity (Ki values in the micromolar range). These results indicate that the PLC-PRF-5 cells express the angiotensin AT1 receptor subtype. This was further supported by the demonstration of the sensitivity of the receptor to dithiothreitol (DTT). Pretreatment of membranes with DTT reduced [3H]AII binding in a concentration-dependent manner with an IC50 of 4.2 +/- 0.9 mM. The coupling of the AT1 receptor to signal transduction pathways was investigated. In intact cells AII (100 nM) evoked an increase in intracellular calcium ([Ca2+]i). This increase in [Ca2+]i was unaffected by PD 123177 (100 microM) but was abolished by DuP 753 (100 microM). Furthermore, AII (100 nM) did not inhibit forskolin (0.1-10 microM) stimulated cyclic AMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the angiotensin II receptor expressed by the human hepatoma cell line, PLC-PRF-5. 133 15

Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors.
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PMID:Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells. 133 86


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