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

Development of specific angiotensin II receptor ligands has recently provided evidence for the existence of two angiotensin II receptor subtypes, termed AT1 and AT2, which differ in their signal transduction mechanisms and in the effects they mediate. In brain, both receptor subtypes are present. Most of the known central actions of angiotensin II, for example the regulation of blood pressure and of electrolyte and water balance, seem to be mediated by the AT1 receptor, while the role of the AT2 receptor is still an enigma. This review by Thomas Unger and colleagues summarizes the current knowledge and latest hypotheses in this rapidly developing field.
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PMID:Angiotensin receptor subtypes in the brain. 152 81

Angiotensin (AII) is associated with increased vascular smooth muscle growth and we have found increased levels of tissue AII during healing of wounded skin. Here we have determined changes in skin AII receptors during wound healing in adult male Sprague-Dawley rats. An abdominal surgical incision was made under anesthesia and rats were sacrificed at different times after wounding. Specific binding of 125I-AII was significantly decreased at 12, 18 and 24 hours in the wounded tissue compared to control tissue from the same rat. By 3 days the binding had recovered to baseline levels. Receptors were mostly AT1, with a high and a low affinity site in the skin both in control and healing tissue. The Bmax of the high affinity site was significantly decreased in healing tissue but there was no significant change in Kd. Our results demonstrate that adult rat skin contains predominantly AT1 receptors and also that these receptors are downregulated for 12-24 hours after wounding.
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PMID:Changes in skin angiotensin II receptors in rats during wound healing. 153 Jun 5

The AT1 receptor subtype modulates all of the hemodynamic effects of the vasoactive peptide, angiotensin II. In this report, we investigate the genomic organization of this important receptor. A rat genomic library was screened with fragments from the 5' region of a previously cloned cDNA, pCa18b, encoding the rat AT1 receptor. Two lambda clones were isolated and the hybridizing restriction fragments were sequenced. Comparison of the genomic and cDNA sequences reveals that the rat AT1 receptor has three exons. Two of the exons encode 5' untranslated sequence while the third exon encompasses the entire coding region, a small portion of the 5' untranslated region and the entire 3' untranslated sequence. Further analysis of the genomic sequence 5' to the start site of pCa18b demonstrates typical sequence motifs found in many eukaryotic promoters including a TATA box, a cap site and a potential Sp1 binding site. Southern analysis of genomic DNA indicates that the AT1 receptor subtype represented by pCa18b is encoded by one gene within the rat genome.
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PMID:The genomic organization of the rat AT1 angiotensin receptor. 153 21

Angiotensin II (AII) has been reported to have direct hypertrophic actions in mammalian and avian myocardium. In this study we determined whether AII had receptor-mediated effects on stimulating cardiac hypertrophy independent of mechanical stimuli (increased cardiac afterload) in adult rats. Angiotensin II was infused into Sprague-Dawley rats for 7 and 14 days. Following this infusion, left ventricular mass indexed to body weight (LV/BW) increased 18.6 and 17.3%, respectively, compared with control (saline infused) rats. Administration of the nonpeptide AII receptor antagonist Dup 753 prevented the increase in left ventricular hypertrophy. Blockade of converting enzyme with enalapril maleate and treatment with a vasodilator had no effect on the AII-induced hypertrophy. In this animal model, the cardiac hypertrophy appeared to be independent of cardiac afterload, because normalization of blood pressure with hydralazine did not prevent the AII-induced hypertrophy. These in vivo studies indicate that AII-induced cardiac hypertrophy is mediated through AT1 angiotensin receptors.
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PMID:Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart. Mediation by the AT1 receptor. 153 68

Angiotensin II (AT) receptor subtypes (AT1, selectively displaced by DuP 753, and AT2, selectively displaced by PD123177 and CGP42112A) were characterized by quantitative autoradiography after incubation with the AT agonist 125I-Sar1-AT, in specific brain nuclei of young (2-week-old) rats. Binding to AT1 receptors was sensitive (decreased affinity) to incubation in the presence of guanosine 5'-O-(3-thio)triphosphate (GTP gamma S). Only the AT1 receptors in the paraventricular nucleus were sensitive to pertussis toxin, indicating the possibility of the existence of AT1 receptor subtypes. The sensitivity of AT2 receptors to GTP gamma S was heterogeneous. In the ventral thalamic and medial geniculate nuclei and in the locus coeruleus, binding to AT2 receptors was sensitive to GTP gamma S and to pertussis toxin pretreatment. Conversely, in the inferior olive, binding was insensitive to GTP gamma S and to pertussis toxin pretreatment. We propose the nomenclature of AT2A receptors for those receptors sensitive to guanine nucleotides and pertussis toxin and that of AT2B receptors for those showing no sensitivity to guanine nucleotides or pertussis toxin treatment.
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PMID:Heterogeneity of angiotensin II AT2 receptors in the rat brain. 153 9

To better understand the action of angiotensin II (ANG II) and angiotensin receptor antagonists (ARA) in human kidney, ANG II receptors were characterized by in vitro autoradiography in fetal and adult human renal tissue using 125I-[Sar1-Ile8]ANG II (125I-ANG II), a potent ANG II antagonist. Binding was inhibited with the ARAs DuP 753 and PD 123177, respectively. In adult kidneys (n = 5), binding of 125I-ANG II showed the following characteristics: arterial vessels had dissociation constant (Kd) = 387.6 +/- 29.1 (SD) pM and maximal binding (Bmax) = 41.4 +/- 3.6 fmol/mg tissue equivalent (TE); glomeruli had Kd = 885.7 +/- 217.1 pM and Bmax = 35.5 +/- 8.1 fmol/mg TE; and outer medulla had Kd = 142.1 +/- 52.5 pM and Bmax = 7.7 +/- 2.3 fmol/mg TE. PD 123177 effectively displaced 125I-ANG II only in large preglomerular vessels [half-maximal inhibitory concentration (IC50) = 0.22 +/- 0.1 nM, type 2 receptor (AT2)], whereas DuP 753 displaced only the labeled ligand in glomeruli (IC50 = 0.28 +/- 0.11 nM) and outer medulla (IC50 = 0.39 +/- 0.11 nM, AT1). In fetal kidneys (n = 4), a diffuse 125I-ANG II binding was demonstrated in the medulla (Kd = 36.6 +/- 7.1 pM; Bmax = 25 +/- 3.8 fmol/mg TE) and in the cortex (Kd = 19.5 +/- 8 pM; Bmax = 7.2 +/- 2.2 fmol/mg TE). Both cortical (IC50 = 0.039 +/- 0.019 nM) and medullary binding (IC50 = 0.076 +/- 0.039 nM) could only be displaced by PD 123177.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoradiographic characterization of angiotensin receptor subtypes in fetal and adult human kidney. 153 89

Angiotensin II stimulated a biphasic 1,2-diacylglycerol formation in [3H]arachidonic acid-labelled mesangial cells. In contrast, in cells labelled with [3H]myristic acid, a tracer that preferentially marks phosphatidylcholine, angiotensin II induced a delayed monophasic production of 1,2-diacylglycerol. This delayed peak of 1,2-diacylglycerol generation was associated with a concomitant increase in choline formation, suggesting that stimulation of mesangial cells with angiotensin II causes a phospholipase D-mediated phosphatidylcholine hydrolysis. This conclusion is supported by the observation that angiotensin II stimulated the accumulation of phosphatidylethanol, when ethanol was added to mesangial cells. The production of choline and phosphatidylethanol stimulated by angiotensin II was completely blocked by the angiotensin II AT1 receptor-selective antagonist DuP 753 with an IC50 value of 8 nM, but not by the angiotensin II AT2 receptor selective ligand CGP 42112A. Furthermore, angiotensin(1-7) and angiotensin(1-6) had only weak effects on choline generation. These data clearly indicate that angiotensin II AT1 receptors trigger phospholipase D-mediated phosphatidylcholine hydrolysis in rat mesangial cells.
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PMID:Angiotensin II stimulation of phospholipase D in rat renal mesangial cells is mediated by the AT1 receptor subtype. 154 25

Two angiotensin II (AII) receptor subtypes, AT1 and AT2, have recently been identified based on their relative affinities for selective peptide and nonpeptide antagonists. In the present study we used various AII peptide analogs, the AT1 subtype selective antagonists, DuP 753 and SK&F 108566, and the AT2 subtype selective antagonists, WL-19 and CGP 42112A, to determine whether AII receptor subtypes exist in the kidney. In agreement with previous studies, octapeptide (Sar1,Ile8-AII) and heptapeptide (AIII and Ile8-AIII) AII analogs displaced [125I]AII bound to rat glomerular membranes with similar affinities. However, in membranes derived from cortical tubules and the outer medulla, the heptapeptide analogs were 20-fold less potent in competing with [125I]AII binding than octapeptide analogs. The AT1 subtype selective nonpeptide AII antagonists, DuP 753 and SK&F 108566, totally displaced [125I]AII binding from all three membrane preparations in a monophasic manner with IC50 values in the 5 to 30 nM range. The AT2 selective peptide antagonist, CGP 42112A, had a low affinity in AII three membranes (IC50 = 450-1050 nM), whereas the nonpeptide AT2 selective antagonist, WL-19, had no activity at concentrations up to 10 microM. Dithiothreitol and the nonhydrolyzable GTP analog, 5'-guanylyl-imidodiphosphate, inhibited AII binding to all three membrane preparations. Based on these results, we conclude that the AII receptors located on glomeruli, tubules and in the outer medulla belong to the AT1 subtype, and that the physiologically important renal actions of AII are mediated through activation of AT1 receptors.
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PMID:Characterization of renal angiotensin II receptors using subtype selective antagonists. 154 5

In vitro differentiation of the mouse neuroblastoma-rat glioma hybrid cell line, NG-108-15, with dimethyl sulphoxide (1.5%) and low serum (0.5%), produced a marked increase in the number of angiotensin II receptors, from a level at the limit of sensitivity using labelled angiotensin II with a high specific activity ([125I]angiotensin II), in undifferentiated cells, to a Bmax of 1077 (1070-1268) fmol/mg in 5-day-differentiated cells. The affinity (Kd) of radiolabelled angiotensin II for the receptors in differentiated cells was 8.1 (7.5-10) nM. The recently available selective non-peptide antagonists, DuP 753 and PD 123177 and the peptide analogues of angiotensin II, CGP 42112A and p-aminophenylalanine6 angiotensin II, were used to characterize the angiotensin II receptors by competing for 125I-[Sar1-Ile8]angiotensin II binding to membranes prepared from undifferentiated and differentiated cells. The predominant angiotensin II receptor subtype expressed by undifferentiated cells was AT1 and after differentiation AT2. This change in receptor expression was evident 2 days after initiation of differentiation, was maximal at 4-5 days and was stable for at least 8 days. Administration of angiotensin II induced intracellular Ca2+ mobilization in both undifferentiated and differentiated cells. This was antagonised by the selective AT1 antagonist, DuP 753, indicating an action at the AT1 receptor subtype in both undifferentiated and differentiated cells. The selective AT2 antagonist, PD 123177 was without effect on the angiotensin II induced increase in intracellular Ca2+. This effect of DuP 753 on Ca2+ was specific for angiotensin II since the drug had no effect on bradykinin induced increases in intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of the angiotensin AT2 receptor subtype expression by differentiation of the neuroblastoma x glioma hybrid, NG-108-15. 155 12

The stimulatory effect of angiotensin II (AT) on the accumulation of inositol phosphates and on aldosterone production is abolished by the AT1 selective receptor antagonist DuP753 while PD123177, an AT2 antagonist, is ineffective. Similarly, a depolarizing effect of AT (inhibition of K+/86Rb efflux) is prevented by DuP753. While mediators derived from phospholipase C activation have a central role in the stimulation of aldosterone production by AT, the effect of AT on K+ permeability is mimicked neither by elevation of cytoplasmic [Ca2+] by ionomycin nor by kinase C activation with phorbol ester. Our results suggest that AT stimulates phospholipase C and the subsequent steroid production by glomerulosa cells through AT1 receptors. In addition some events induced by the activation of AT1 receptors may not be mediated by the activation of phospholipase C.
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PMID:Angiotensin II exerts its effect on aldosterone production and potassium permeability through receptor subtype AT1 in rat adrenal glomerulosa cells. 155 76


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