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

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

The role of AII receptors subtypes, AT1 and AT2, in the regulation of aldosterone secretion was studied in adrenal glomerulosa cells and membranes from rats on normal and low sodium intake, using AII receptor subtype-specific antagonists. In adrenal glomerulosa cells, more than 90% of the receptors were AT1 and there was a good correlation between the potencies of the antagonists to inhibit ligand binding, and AII-stimulated aldosterone production and inositol phosphate formation. The inhibition of basal and ACTH-stimulated cAMP by AII was also abolished by the AT1, but not the AT2, antagonist. Sodium restriction for 6 days increased both receptor subtypes in the same proportion, but only the AT1 antagonist inhibited AII-stimulated aldosterone production. The data demonstrate that AT1 receptor mediates the regulatory actions of AII in the adrenal zona glomerulosa.
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PMID:Role of angiotensin II receptor subtypes on the regulation of aldosterone secretion in the adrenal glomerulosa zone in the rat. 133 30

In the present studies, ligand competition experiments were conducted to examine the ability of angiotensin II peptide agonists and nonpeptide AT1- and AT2-selective receptor antagonists to inhibit the binding of [125I]angiotensin II to bovine adrenal cortical membranes. Angiotensin II, angiotensin III, the All-(3-8) hexapeptide fragment of angiotensin II, and the AT1-selective receptor antagonist L-158,809, inhibited [125I]angiotensin II binding in a biphasic fashion indicative of a ligand interaction at more than one recognition site. Approximately 20% of low affinity [125I]angiotensin II binding was inhibited only by high micromolar concentrations of L-158,809. RG 13647 (1(-1,4-benzodioxan-2-methyl)-5-diphenylacetyl-4,5,6,7-tetra hydro-1H-imidazo- [4,5,c]-pyridine-6-carboxylic acid) represents a potent and AT2-selective analog of PD 123177 and showed weak activity in competing for [125I]angiotensin II binding with an IC50 value of 100 microM. When subsequent competition studies were conducted in the presence of 1 microM L-158,809 to block [125I]angiotensin II to the AT1 receptor subtype, the angiotensin II agonists produced monophasic inhibition curves with AII-(3-8) showing the greatest activity (IC50 = 6 nM) followed by angiotensin III (IC50 = 15 nM) much greater than angiotensin II (IC50 = 110 nM). RG 13647 was not found to significantly inhibit this portion of [125I]angiotensin II binding. These data demonstrate that bovine adrenal cortex contains both the AT1 receptor subtype, as well as, a novel class of [125I]angiotensin II recognition sites which may be analogous to the recently described angiotensin IV (AT4) receptor.
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PMID:The angiotensin hexapeptide 3-8 fragment potently inhibits [125I]angiotensin II binding to non-AT1 or -AT2 recognition sites in bovine adrenal cortex. 142 57

We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from many species. The binding site is pharmacologically distinct from the classic angiotensin receptors (AT1 or AT2) displaying low affinity for the known agonists (AII and AIII) and antagonist (Sar1,Ile8-AII). Although a definitive function has not been assigned to this system in many of the tissues in which it resides, AIV's interaction with endothelial cells may involve a role in endothelial cell-dependent vasodilation. Consequent to this action, AIV is a potent stimulator of renal cortical blood flow.
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PMID:Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor. 143 83

A unique angiotensin binding site specific for the hexapeptide, AII(3-8), has been identified in guinea pig hippocampus. This binding site, which is present in the pyramidal cell layer of CA1, CA2, CA3 of the hippocampus and dentate gyrus, binds AII(3-8) with high affinity (KD = 1.29 +/- 0.18 nM) in a saturable manner (Bmax = 449 +/- 62 fmol/mg protein). The N-terminal structure of the binding ligand is paramount in determining the binding affinity. The C-terminal requirements seem less stringent as evidenced by the binding affinity of AII(3-7) (KD = 20.9 +/- 2.1 nM). Neither AII, AIII,Sar1, Ile8-AII, Dup 753 nor CGP42112A appear to bind, indicating that this binding site is neither the AT1 nor AT2 sites described for AII/AIII. Autoradiographic analysis of hippocampus binding confirms the inability of Sar1,Ile8-AII to compete for [125I]AII(3-8) binding. Conversely AII(3-8) was unable to displace [125I]Sar1,Ile8-AII binding.
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PMID:Identification of an AII(3-8) [AIV] binding site in guinea pig hippocampus. 150 42

Membrane angiotensin II receptors were measured in trophoblastic tissues using a 2-step procedure. The first step consisted of the relative measurement performed at a fixed 125I[Sar1 Ile8]AII concentration of 0.15 nM in order to determine which tissues had a sufficient number of binding sites for studying the competition curves. The second consisted of determining the maximal binding (Bmax) and the dissociation constant (Kd) for [Sar1 Ile8] AII and the receptor subtypes in these tissues. The relative binding measurement revealed a significant number of occupied sites in rabbit fetal placenta and chorion (159 +/- 17 and 51 +/- 10 fmol/mg proteins) and in guinea pig chorion (132 +/- 12). The mean values of the other trophoblastic tissues were 3-10-fold lower in the 2 species. The competition curves obtained from tissues with high angiotensin II binding receptors showed the predominance of the AT2 subtype in rabbit fetal placenta (AT1/AT2 = 25/75) and of the AT1 receptor in guinea pig chorion (97/3) and in rabbit chorion (90/10). The [SAR1 Ile8] AII affinity (Kd) obtained from Scatchard plot analysis was 1.2 +/- 0.2 nM (n = 5) in fetal placenta and 1.2 (n = 1) in rabbit chorion and 0.5 +/- 0.1 (n = 3) in guinea pig chorion. In these tissues, the respective Bmax values were 1,281 +/- 115 (n = 5), 263 (n = 1) and 1,188 +/- 134 fmol/mg proteins (n = 3). These findings indicate that rabbit fetal placenta and chorion and guinea pig chorion are the most important sites of action for the renin-angiotensin system present in trophoblastic tissues.
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PMID:[Identification of angiotensin II receptor and determination of its subtypes in rabbit and guinea pig fetal tissue]. 157 5

The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway.
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PMID:Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. 159 49

High-affinity receptors for angiotensin II were identified on Xenopus laevis cardiac membranes and characterized by binding-inhibition studies with peptide and non-peptide AII antagonists. Scatchard analysis of the binding data identified a high-affinity site with Kd1 = 1.6 nM and Bmax1 = 3.7 pmol/mg protein and a low-affinity site with Kd2 = 22 nM and Bmax 2 = 9.5 pmol/mg protein. Treatment with dithiothreitol reduced the number of binding sites by greater than 70%. The rank order of potency for ALL analogs was (agent, IC50) [Sar1,Ile8]AII, 0.91 nM greater than AII, 2.0 nM greater than AI, 5.3 nM greater than [Sar1, Ala8]AII, 19 nM much greater than CGP42112A, 1.2 microM much much greater than DuP 753 approximately PD-123177, greater than 100 microM. The relative potencies of these compounds differ markedly from their activities on the two known mammalian AII receptor subtypes, AT1 and AT2. These results indicate that amphibian AII receptors are pharmacologically distinct from both the AT1 and AT2 receptors characterized in mammalian tissues.
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PMID:Amphibian myocardial angiotensin II receptors are distinct from mammalian AT1 and AT2 receptor subtypes. 206 Jun 51

The deoxynucleoside 5'-triphosphate (dNTP) pool sizes have been determined before and after electron (e-) irradiation in sets of radiation sensitive and resistant cell lines. In the L5178Y mouse lymphoma radiosensitive line (LS), the dTTP pool fell 50% following irradiation, whilst the three other dNTP pools remained unaltered. On the other hand, for the radioresistant line (AII) all four dNTP pools increased by 2-to 3-fold. The dNTP pools of the Chinese hamster radiosensitive (V79) line and radioresistant (V79/79) lines were unaltered by the radiation, but a difference in pool size was present before irradiation, with the pools of the V79 cells being approximately twice those of the V79/79 cells. Two out of the three ataxia telangiectasia cell lines studied show reduced dNTP pools when compared with those of normal human fibroblasts and these pools were also unaltered by the radiation. In the L5178Y and Chinese hamster cells the levels of enzymes involved in the biosynthesis of dNTPs have been determined. In general the higher the level of ribonucleoside diphosphate reductase (RDR) the larger the cellular pools. The observed levels of RDR could, in part, explain the observed results. Increasing the dTTP pool by the addition of deoxythymidine and deoxycytidine to the cell culture with the V79/79 cells reduced their sensitivity to the radiation. These results indicate a relationship between a cell's sensitivity to e- irradiation and the sizes of the cellular dNTP pools. However, the exact nature of any such relationship is unknown.
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PMID:The sizes of cellular deoxynucleoside 5'-triphosphate pools in relation to sensitivity to electron irradiation using sensitive and resistant cell lines. 381 36

Glomerular mesangial cells and cardiac fibroblasts have been called "myofibroblasts" because of their phenotypic characteristics (resembling both the fibroblast and muscle cells). Thus, it is not surprising that AII would have similar effects on both cell types, which play critical roles in target organ stress response and wound healing, ultimately leading to remodeling changes. These effects are primarily mediated by the AT1 receptor and include: 1) growth: hyperplasia in cardiac fibroblasts and hypertrophy in normal adult mesangial cells and 2) matrix production: there appears to be an early upregulation of fibronectin message which is later followed by an increase in collagens. It is likely that elevated production of fibronectin may activate signal transduction pathways which lead to increased expression of collagen genes, and which may be critical for the organization and laying down of collagens. Thus, an overall theme that emerges is the impact of AII on both growth and wound repair. Other potential important cellular effects of AII in these systems include: 1) stimulation of growth factors, cytokines, and arachidonic acid products that could have autocrine or paracrine effects, 2) regulation of cell migration and adhesion, 3) alteration of responses to neurohormones, 4) development and maintenance of a differentiated phenotype, and others. Molecular techniques including subtraction hybridization, differential display, antisense knockout, and development of transgenic and embryonic stem cell models will be important in defining the specific role of AII in cardiovascular and renal disease.
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PMID:Angiotensin II in cell growth and matrix production. 748 24


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