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

Membrane angiotensin II receptors were measured in human placenta by means of 125I [Sar1 Ile8] All (angiotensin II antagonist) and characterized by using 2 other antagonists of angiotensin II: Dup 753 and CGP 42112A. These are specific and selective ligands which enable identification of AT1 and AT2 receptor subtypes respectively. The [Sar1 Ile8] All affinity is similar (Kd approximately 1 nmol.l-1) in the 3 different placental structures examined. However, the Bmax of villous tissues is approximately 9 times higher than that observed in chorionic plate but remains near that found in basal plate. In the central area of the placenta, mean values of 125I [Sar1 Ile8] All binding observed at a single concentration of 0.15 nmol.l-1 are 242 +/- 31 fmol/mg proteins in basal plate, 300 +/- 35 in villous tissues and 36 +/- 8 in chorionic plate. The umbilical vein and arteries respectively have 8.8 +/- 4.8 and 4.0 +/- 1.7 fmol/mg protein. The subtype analysis shows that only AT1 receptor is present in placental tissues. The Bmax values as well as those obtained by the relative measurement performed at a fixed 125I [Sar1 Ile8] All concentration of 0.15 nmol.l-1 indicate that the highest concentrations of angiotensin II receptors are found in placental villous tissues.
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PMID:[Angiotensin II receptors in the human placenta are type AT1]. 187 51

Both neurons and astrocytes contain specific receptors for angiotensin II (AII). We used selective ligands for the AT1 and AT2 types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of 125I-labeled AII (125I-AII) specific binding with AT1 (DuP753) or AT2 (PD123177, CGP42112A, [Phe(p-NH2)6]AII) selective receptor ligands revealed a potency series of AII greater than DuP753 much greater than CGP42112A greater than [Phe(p-NH2)6]AII greater than PD123177. These results suggest a predominance of the AT1 receptor subtype in neonatal astrocytes. Also, in astrocyte cultures, AII stimulated increases in inositolphospholipid hydrolysis that were significantly reduced by the AT1 receptor antagonist DuP753 but not altered by the AT2 receptor antagonist PD123177. In neonatal neuron cultures, competition of 125I-AII specific binding with the above ligands revealed a potency series of CGP42112A = AII greater than [Phe(p- NH2)6]AII greater than PD123177 much greater than DuP753. 125I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 microM PD123177, and the residual 125I-AII specific binding was eliminated by DuP753. Also, in neuron cultures, AII induced decreases in basal cGMP that were completely blocked by PD123177 or CGP42112A but not by DuP753. Our results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT1 receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT2 receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT1 receptors is also present in these neurons.
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PMID:Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain. 188 96

Angiotensin II is known primarily for its effects on blood pressure and electrolyte homeostasis, but recent studies suggest that angiotensin II may play a role in the regulation of cellular growth. This study was undertaken to identify the angiotensin II receptor subtypes expressed during fetal and neonatal development and to characterize their cellular localization. Using an in situ receptor binding assay on sagittal frozen sections of fetal and neonatal rats, bound 125I-[Sar1,Ile8]-angiotensin II was visualized by film and emulsion autoradiography. Bound radioligand was detected by E11 (embryonic day 11) and maximal binding occurred by E19-21. Radioligand binding remained unaltered 30 min after birth, whereas a noticeable and stable decrease was observed 12 h postparturition. The highly abundant angiotensin II receptors were shown to be AT2 by the marked reduction in radioligand binding achieved with PD123177 (10(-7)M), a specific AT2 receptor antagonist, whereas DuP 753 (10(-5)M), an AT1 receptor antagonist, had little effect. Emulsion autoradiography showed radioligand binding in the undifferentiated mesenchyme of the submucosal layers of the intestine and stomach, connective tissue and choroid surrounding the retina, subdermal mesenchyme adjacent to developing cartilage, diaphragm, and tongue. Residual AT2 receptors were found on the dorsal subdermal region of the tongue 72 h after birth. AT1 receptors were detected in the placenta at E13 and in the aorta, kidney, lung, liver, and adrenal gland at E19-21, consistent with an adult distribution. The transient expression of AT2 receptors in the mesenchyme of the fetus suggests a role of angiotensin II in fetal development.
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PMID:Expression of AT2 receptors in the developing rat fetus. 188 77

Quantitative autoradiography using the agonist 125I-Sar1-angiotensin II was used to localize and characterize angiotensin II (AT) receptors in the anterior cerebral artery of the male rat. This artery showed a moderately high number of AT receptors, localized throughout the arterial wall. The number of receptors was higher (125 +/- 7 fmol/mg protein) in arteries from young 2-wk-old rats compared with those in adult 8-wk-old rats (43 +/- 2 fmol/mg protein). In the anterior cerebral artery, AT binding was insensitive to displacement with the selective AT1 antagonist DuP 753 but was readily displaced by the selective AT2 antagonist CGP-42112 A (concentration eliciting 50% of maximum inhibition: 6 +/- 1 x 10(-10) M). This indicated that the AT receptors in the cerebral artery were of the AT2 subtype. Our observations suggest that AT may exert its effects on cerebral circulation by stimulation of AT2 receptors and that these receptors may play a role during cerebrovascular development.
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PMID:Characterization of AT2 angiotensin II receptors in rat anterior cerebral arteries. 188 16

Binding sites for angiotensin II were found, in a line of Swiss 3T3 cells (designated as R3T3 cells), that were insensitive to Dup 753 and dithiothreitol yet were sensitive to PD 123319, making them members of the AT2 class of angiotensin II binding sites. These binding sites appeared not to be coupled to guanine nucleotide-binding proteins, and affinity labeling experiments revealed a specifically labeled protein with an apparent molecular weight of about 100,000. Treatment of cells with angiotensin II revealed no perturbation of common signaling pathways, including stimulation of phosphatidylinositol turnover, effects on levels of cAMP, tyrosine kinase activity, and release of arachidonic acid. Also, angiotensin II or PD 123319 had no effect on cell growth, mitogenesis, or hypertrophy or on mitogenesis or hypertrophy stimulated by several growth factors. These results show that the AT2 binding site is quite distinct from the AT1 site in terms of molecular weight, binding properties, and coupling to second messenger systems. Although the significance of this novel angiotensin II binding site remains obscure, the identification of cell lines selectively expressing it should greatly aid in the understanding of its regulation and function.
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PMID:Characterization of angiotensin II (AT2) binding sites in R3T3 cells. 189 25

We have studied the effect of GTP gamma S on the affinity and binding kinetics of angiotensin II in plasma membrane particulate prepared from tissues expressing either only AT1 (human renal artery smooth muscle cells), only AT2 (human myometrium and bovine cerebellar cortex) or both angiotensin II receptor subtypes (rat adrenal glomerulosa). We also examined the ability of angiotensin II to stimulate GTP gamma[35S] incorporation in these membrane preparations. In contrast to its effects on angiotensin II binding to the AT1 receptor, GTP gamma S does not affect binding parameters to the AT2 receptor. Moreover, in tissues expressing solely AT2 receptors, angiotensin II was unable to induce GTP gamma[35S] incorporation. These findings indicate that AT2 receptors do not interact with G-proteins and that angiotensin II must therefore mediate some of its effects through G-protein-independent mechanisms.
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PMID:Angiotensin II AT2 receptors do not interact with guanine nucleotide binding proteins. 190 81

Quantitative autoradiography was used to characterize angiotensin AT1 and AT2 receptors, in the rat aorta at three developmental ages; embryonic day 18 (E18), and postnatal weeks 2 and 8. The expression of angiotensin receptors was higher in the aorta of E18 and 2-week-old rat. A major proportion of the angiotensin receptors expressed in the aorta at these two ages was AT2 (84 and 81% respectively). Conversely, in the aorta of 8-week-old rats, AT1 was the predominant angiotensin receptor subtype (71%). In 8-week-old rats, the AT2 subtype was also present (28%). In pre- and postnatal rats, [125I]Sar1-angiotensin II binding to AT1 receptors was sensitive to GTP gamma S whereas binding to AT2 receptors was not. AT2 receptors may serve an important role during stages of rapid growth of the aorta, and also have a significant function in the adult vasculature.
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PMID:Changes in expression of angiotensin receptor subtypes in the rat aorta during development. 193 Jan 81

DuP 532 (2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl- 4-yl)methyl]imidazole-5-carboxylic acid) inhibited the specific binding of [125I]angiotensin II (AII) for the subtype receptor AT1 in rat adrenal cortical membranes with an IC50 of 3.1 X 10(-9) M, but not the [125I]AII binding for the subtype AT2 sites in rat adrenal medulla tissues. It inhibited the contractile response to AII selectively and noncompetitively in the isolated rabbit aorta with a KB value of 1.1 X 10(-10) M. The selective AII antagonism was confirmed in the guinea pig ileum and the pithed rat. In conscious rats, DuP 532 inhibited the AII-induced pressor effect, aldosterone secretion, and water drinking induced by AII. In conscious renal hypertensive rats, DuP 532 decreased blood pressure with i.v. and p.o. ED30 of 0.02 and 0.21 mg/kg, respectively. The antihypertensive effect of DuP 532 at 0.3 to 3 mg/kg p.o. lasted for at least 24 hr. In conscious spontaneously hypertensive rats, DuP 532 given i.v. or p.o. at 0.3 to 3 mg/kg reduced blood pressure dose-dependently. DuP 532, at doses up to 100 mg/kg i.v., did not cause a pressor response in conscious normotensive rats, suggesting lack of agonism. DuP 532 exerted selective AII antagonism in conscious dogs. In conscious furosemide-treated dogs, DuP 532 given either at 0.3 and 1 mg/kg i.v. or at 1 to 10 mg/kg p.o. decreased blood pressure. As the AT1 receptors are responsible for AII-induced vasoconstriction, aldosterone secretion, and water drinking, our study indicates that DuP 532 is a potent, orally active, selective, and noncompetitive AT1 receptor antagonist and antihypertensive agent.
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PMID:Pharmacology of DuP 532, a selective and noncompetitive AT1 receptor antagonist. 194 32

The displacement of [125I]Sar1, Ile8 angiotensin II binding by the receptor subtype selective angiotensin II antagonists, DuP-753 and WL-19 (PD121981) was used to define the relative proportion of angiotensin subtype AT1 and subtype AT2 receptors, respectively in various tissues (aorta, heart, adrenal cortex, kidney cortex and brain) of the rat, rabbit and monkey. The relative abundance of these receptor subtypes varied greatly not only among different tissues of the same species but also within the same tissue of different species. The relative affinity of the DuP-753 and WL-19 for the angiotensin receptor subtypes did not vary markedly suggesting that the two angiotensin receptor subtypes in these tissues and species are similar.
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PMID:Angiotensin receptor subtypes in rat, rabbit and monkey tissues: relative distribution and species dependency. 194 52

We used quantitative autoradiography to characterize angiotensin-II (ANG-II) receptor subtypes in areas of the rat basal forebrain involved in pituitary control. ANG binding was totally displaced by the selective AT1 receptor subtype antagonist DuP 753 and was inhibited by dithiothreitol in median eminence, infundibular stem, paraventricular nucleus, subfornical organ, median preoptic nucleus, anterior pituitary, and the forebrain ANG-II receptor band, which extends from the subfornical organ to the vascular organ of the lamina terminalis, including the lamina terminalis and a continuous band of receptors reaching the paraventricular nucleus. In these areas, binding was not affected by the selective AT2 competitors PD 123177 or CGP 42112 A, indicating the presence of AT1 and the absence of AT2 receptors. AT1 binding was higher in the external layer and lateral parts of the median eminence. Conversely, ANG binding in the dura mater encapsulating the pituitary, in the vessels adjacent to this part of the dura mater, presumably branches of the hypophyseal arteries, and in anterior cerebral arteries was displaced by PD 123177 and CGP 42112 A, and was unaffected by dithiothreitol or DuP 753, indicating the presence of AT2 receptors in these structures. Our results implicate AT1 receptors in the central neural regulation of pituitary function. AT2 receptors may play a role in the regulation of blood flow to the basal forebrain and the pituitary gland.
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PMID:Angiotensin-II receptor subtypes in median eminence and basal forebrain areas involved in regulation of pituitary function. 195 84


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