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

Angiotensin II is an important effector molecule controlling blood pressure and volume in the cardiovascular system. Its importance is manifested by the efficacy of angiotensin-converting enzyme inhibitors in the treatment of hypertension and congestive heart failure. Angiotensin II interacts with two pharmacologically distinct subtypes of cell-surface receptors, AT1 and AT2. AT1 receptors seem to mediate the major cardiovascular effects of angiotensin II. Here we report the isolation by expression cloning of a complementary DNA encoding a unique protein with the pharmacological specificity of a vascular AT1 receptor. Hydropathic modelling of the deduced protein suggests that it shares the seven-transmembrane-region motif with the G protein-coupled receptor superfamily. Knowledge of the AT1 receptor primary sequence should now permit structural analysis, definition of the angiotensin II receptor gene family and delineation of the contribution of AT receptors to the genetic component of hypertension.
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PMID:Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. 204 70

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

Thymic epithelial reticulum (TER) cell lines were established from thymuses of a young healthy AKR mouse (A2T), a preleukemic AKR mouse (A6T), and two lymphoma-bearing AKR/Ms mice (ASLT-1 and ASLT-2). Numerous type-C virus particles with occasional budding forms were observed in all cell lines. Expression of XC-detectable, N-tropic, ecotropic virus was observed in every cell line, whereas the presence of xenotropic and mink cell focus-inducing (MCF) viruses could be detected only in TER cells derived from preleukemic and leukemic mice. Expression of xenotropic virus in various cells of newborn and young AKR mice could readily be induced by IUdR treatment, whereas MCF virus was never detected in these cells, with the exception of the A2T cell line after more than 20 passages, in which MCF virus with dual-tropic infectivity emerged in addition to ecotropic and xenotropic viruses. These spontaneous and induced MCF viruses were purified, and their virological properties were characterized. The cloned MCF viruses (MCFs AT1, AT2, AT3, and AT4-IU) showed dual tropism and produced cytopathic effect-like foci in mink lung cells. Preinfection with either ecotropic or xenotropic virus interfered with the infectivity of MCF viruses. Spontaneous leukemogenesis in AKR mice was accelerated by the inoculation of MCF viruses. These findings indicate that TER cells could serve as the host cells for the genetic recombination of the endogenous MuLV; the recombinant MuLV, MCF virus, appears to be most closely associated with leukemogenesis in AKR mice.
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PMID:In vitro studies of the mechanism of leukemogenesis. II. Characterization of endogenous murine leukemia viruses isolated from AKR thymic epithelial reticulum cell lines. 628 54

The anaerobic threshold during graded exercise (GXT, AT1) was determined as the exercise level initiating a curvilinear increase in ventilation (VE), and during prolonged exercise (PXT, 40 min, AT2) as the maximal exercise level where still a steady state for VE can be reached. Subjects were 8 healthy males, 20 to 53 years of age. Maximal exercise capacity was estimated by means of 1) VO2 max 2) max time on bicycle ergometer at 200 Watts and 3) maximal distance run within 12 min (Cooper test). VO2 max was significantly related to AT1, GXT (r = 0.85, 0.01 less than p less than 0.001) and to AT2, PXT (r = 0.75, 0.05 less than p less than 0.01). Also a significant correlation was found between the endurance exercise capacity (= 200 Watts) and both AT1 (r = 0.80; 0.05 less than p less than 0.01) and AT2 (r = 0.84; 0.01 less than p less than 0.001). Finally only AT2 was significantly correlated with the Cooper test (r = 0.81; 0.01 less than p less than 0.001), no significant relationship was found for AT1 (r = 0.68; p less than 0.05). In conclusion AT1 reached the highest correlation with a short maximal exercise test such as VO2 max, in contrast to AT2, which showed the highest correlation with endurance exercise such as Cooper test or maximal exercise time at 200 Watts.
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PMID:Anaerobic threshold for long-term exercise and maximal exercise performance. 681 29

From Aspergillus fumigatus I-21 (ATCC 32722), which grows at temperatures from 12 to 50 degrees C, three multistep, independently derived, cold-sensitive mutants unable to grow at 37 degrees C or below (Cs-37) were obtained by sequential exposure to ethylmethane sulfonate (strain AT2) or N-methyl-N'-nitro-N-nitrosoguanidine (AT1 and AT3). These mutants and ON5, a five-step Cs-37 mutant, were marked by mutations affecting spore color and nutritional requirements and crossed in four combinations by classical parasexual means. The heterokaryons demonstrated partial complementation with respect to auxotrophic requirements (suboptimal growth on minimal medium) and cold sensitivity (growth at 37 degrees C but not at 25 degrees C). Most presumed diploids, formed by exposure of the heterokaryons to d-camphor vapors, showed complete complementation but were unstable, as demonstrated by variations in spore sizes and markedly different ratios of segregant classes derived from different clones. Analysis of the segregants of the diploids or aneuploids, induced by Benomyl, indicated that multiple genes were responsible for cold sensitivity in each Cs-37 mutant, since segregants with various levels of cold sensitivity were obtained. The higher than predicted frequency of reversion to temperatures two or more steps back in the sequence of cold sensitivity mutations suggested that these genes or their products interacted. No Cs-37 segregant yielding a consistently lower frequency of revertants than the original mutants was obtained.
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PMID:Sequential cold-sensitive mutations in Aspergillus fumigatus. II. Analysis by the parasexual cycle. 701 81

During this study the relationships between venous lactate concentration and accociated changes in respiratory gas exchange were investigated. Five men performed two successive incremental exercise tests to exhaustion on an electronically braked cycle ergometer. These tests were separated by a 5 min rest period. During the initial test venous lactate concentrations showed a characteristic curvilinear increase and the anaerobic threshold (AT1) was determined conventionally. During the second test lactate concentrations were still decreasing at higher work rates than the AT1, and a second anaerobic threshold (AT2) was determined as the point where lactate concentrations again increased. The departure from linearity of the ventilatory response to both exercise tests occurred at a similar work rate, irrespective of whether venous lactate concentrations were increasing or decreasing. Carbon dioxide production was similar during the two exercise tests. The anaerobic thresholds as determined by respiratory gas analysis (ATR) were therefore similar for both tests. Results of this study indicate that changing venous lactate concentrations were not responsible for the ventilatory drive which occurred at the ATR. The venous lactate response to work at a constant rate determined within the range AT1-AT2 was also investigated. It was concluded that the lactate response to constant work rate will vary predictably at work rates falling within the AT1 to AT2 range. At AT1 no increase in venous lactate concentrations occurred, while at AT2 these increased progressively, and the test was terminated at varying times (12-15 min) due to subject exhaustion. At work rates determined from the ATR venous lactate concentrations varied according to the placement of the ATR within the AT1 AT2 range.
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PMID:The anaerobic threshold as determined before and during lactic acidosis. 719 14

Angiotensin II, a potent regulator of blood pressure and of water and electrolyte balance, binds to two different G-protein-coupled receptors. The type-1 receptor (AT1) mediates the vasopressive and aldosterone-secreting effects of angiotensin II, but the function of the type-2 receptor (AT2) is unknown, although it is expressed in both adult and embryonic life. To address this question, we have generated mice lacking the gene encoding the AT2 receptor. Mutant mice develop normally, but have an impaired drinking response to water deprivation as well as a reduction in spontaneous movements. Their baseline blood pressure is normal, but they show an increased vasopressor response to injection of angiotensin II. Thus, although the AT2 receptor is not required for embryonic development, it plays a role in the central nervous system and cardiovascular functions that are mediated by the renin-angiotensin system.
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PMID:Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. 747 66

There are two major angiotensin II receptor isoforms, AT1 and AT2. AT1 mediates the well-known pressor and mitogenic effects of angiotensin II, but the signalling mechanism and physiological role of AT2 has not been established. Its abundant expression in fetal tissues and certain brain nuclei suggest possible roles in growth, development and neuronal functions. Here we report the unexpected finding that the targeted disruption of the mouse AT2 gene resulted in a significant increase in blood pressure and increased sensitivity to the pressor action of angiotensin II. Thus AT2 mediates a depressor effect and antagonizes the AT1-mediated pressor action of angiotensin II. In addition, disruption of the AT2 gene attenuated exploratory behaviour and lowered body temperature. Our results show that angiotensin II activates AT1 and AT2, which have mutually counteracting haemodynamic effects, and that AT2 regulates central nervous system functions, including behaviour.
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PMID:Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. 747 67

The AR42J acinar cell line was characterized as a potential cellular model to assess the functional aspects of an exocrine pancreatic angiotensin system. Binding studies revealed that the AR42J cells express high affinity angiotensin II binding sites (Kd = 0.73 +/- 0.06 nM; Bmax = 292 +/- 15 fmol/mg protein, n = 3). Competition studies established that these cells, similar to the intact pancreas, express predominantly the AT2 receptor subtype. The AT2-selective antagonists CGP 42112A, PD 123177, and PD 123319 competed for the majority of angiotensin II binding. However, 10-15% of the angiotensin II binding sites were competed for by the AT1-selective antagonist DuP 753 (Losartan). Affinity labeling of these binding sites with [125I]angiotensin II followed by SDS gel electrophoresis under reducing conditions revealed a single band comprising a molecular mass of 108,000 Da. Competition with unlabeled angiotensin II or the AT2 antagonist, but not the AT1 antagonist, abolished the 108,000-Da band. In intact cells, angiotensin II caused a rapid increase in intracellular calcium (Ca2+) using Fura-2 as a Ca2+ indicator. Pretreatment of the cells with the AT1 antagonist DuP 753 completely inhibited the angiotensin II-induced rise in Ca2+; however, the AT2 antagonists CGP 42112A and PD 123177 were ineffective in blocking the Ca2+ increase. These results demonstrate that this pancreatic acinar cell line expresses both AT2 and AT1 angiotensin II receptor subtypes. The AT1 receptor is coupled to the mobilization of Ca(2+)--a characteristic shared by AT1 receptors in other tissues.
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PMID:Characterization of angiotensin II receptor subtypes in pancreatic acinar AR42J cells. 747 11

The type 1 angiotensin II (AT1) receptor is well characterized but the type 2 (AT2) receptor remains an enigma. We tested the hypothesis that the AT2 receptor can modulate the growth of vascular smooth muscle cells by transfecting an AT2 receptor expression vector into the balloon-injured rat carotid artery and observed that overexpression of the AT2 receptor attenuated neointimal formation. In cultured smooth muscle cells, AT2 receptor transfection reduced proliferation and inhibited mitogen-activated protein kinase activity. Furthermore, we demonstrated that the AT2 receptor mediated the developmentally regulated decrease in aortic DNA synthesis at the latter stages of gestation. These results suggest that the AT2 receptor exerts an antiproliferative effect, counteracting the growth action of AT1 receptor.
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PMID:The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. 747 61


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