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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 used whole-cell, voltage-clamp procedures to determine the effects of angiotensin II (AII) on net outward current (I(no)) in neurons co-cultured from the hypothalamus and brainstem of 1-day-old rats. Ino is the sum of all inward and outward membrane currents (minus Na+, which is blocked by tetrodotoxin) which occur during the repolarization phase of the action potential. We have determined that AII elicits two separate effects on I(no) in cultured neurons. AII caused a reversible and concentration (0.1 nM-10 microM)-dependent increase in I(no). This effect is inhibited by the AT2 receptor-selective antagonists, PD123177 and PD123319 (both 100 nM), but not by the AT1-selective receptor blocker, DuP753 (Losartan; 100 nM), and so it is mediated by AT2 receptors. In a smaller number of neurons AII induced a reversible and concentration (0.01 nM-10 microM)-dependent decrease in I(no) that was blocked by Losartan (100 nM) but not by PD123177 (100 nM). Thus the decrease in I(no) is mediated by AT1 receptors. Additionally, some neurons displayed both AT1- and AT2 receptor-mediated effects on I(no). Our results demonstrate two distinct actions of AII on membrane ionic currents in cultured neurons, effects that are mediated by different AII receptor subtypes.
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PMID:Modulation of net outward current in cultured neurons by angiotensin II: involvement of AT1 and AT2 receptors. 150 8

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

Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It acts through at least two types of receptors termed AT1 and AT2. We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1. The human AT1 gene was mapped to chromosome 3q by polymerase chain reaction analysis of DNA from a panel of human-hamster somatic cell hybrids. The predicted amino acid sequence is 95% identical to the corresponding rat and bovine receptors and 25% and 22% identical, respectively, to the receptors encoded by the RTA and MAS genes. Characterization of several human cDNA clones demonstrated the existence of two alternate 5'-untranslated regions (UTRs) that contain a common initial sequence but differ by the presence or absence of an insertion of 84 base pairs. In the genomic sequence, the coding sequences are contained in a single exon, with an intron occurring in the 5'-UTR at the position of insertion of the 84-base pair sequence. The exons encoding the alternate 5'-UTRs are located at least 3.8 kilobases away from the exon encoding the protein. Reverse transcription-polymerase chain reaction analysis showed that both forms of 5'-UTR are present in approximately equal abundance in a range of tissues expressing AT1. The reagents developed in this work may be useful in testing the hypothesis that genetic variations in angiotensin II receptor function are associated with a tendency to develop hypertension.
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PMID:Genetic analysis of the human type-1 angiotensin II receptor. 150 24

Although angiotensin II (Ang II) binding sites have been extensively investigated in brain, revealing the presence of both AT1 and AT2 subtypes in various areas, the question as to which cells express AT1 and AT2 sites is still open. We report here that primary cultures of astrocytes obtained from various brain regions of fetal (F17) and one-day-old rats express Ang II binding sites belonging only to the AT1 subtype. The binding sites have the same binding profile in all regions tested; however, much less binding was observed in membranes of astrocytes derived from cortical than from subcortical regions and almost none were found in neonatal cortex. In addition, the dispersion method used at the onset of culture affects the number of binding sites present at the end of the culture period.
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PMID:Characterization and distribution of angiotensin II binding sites in fetal and neonatal astrocytes from different rat brain regions. 151 22

Both angiotensin II (ANG II) and angiotensin III (ANG III) administered centrally produce drinking and increases in blood pressure. The recent characterization of two subtypes for the ANG II receptor, the AT1 and AT2, raises the questions of whether drinking and pressor responses to ANG II can be separated pharmacologically and whether ANG III acts via the same receptor subtype. Therefore, the current study examined drinking and blood pressure responses to ANG II and ANG III administered centrally in adult male Sprague-Dawley rats in the presence or absence of a selective AT1 receptor antagonist. Blockade of the AT1 receptor abolished both drinking and pressor responses to ANG II and ANG III. However, drinking to the cholinergic agonist, carbachol, was unaffected. These results demonstrate that centrally administered ANG II and ANG III increase both water intake and blood pressure via the AT1 receptor subtype.
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PMID:Effects of a non-peptide angiotensin receptor antagonist on drinking and blood pressure responses to centrally administered angiotensins in the rat. 151 29

Soluble angiotensin-binding protein (sABP) is a 75-kDa cytosolic protein that binds angiotensins and its analogues with high affinity. In this study, the primary structure of porcine sABP is determined by cDNA cloning. Based on the partial amino acid sequences of sABP tryptic fragments, fully degenerate oligonucleotides were synthesized, and used as primers for polymerase chain reactions to amplify the corresponding sABP cDNA fragment from porcine liver first-strand cDNA. By using initially the polymerase chain reaction product and later partial cDNA clones as probes, porcine heart and liver cDNA libraries were screened, and several positive clones were obtained including one covering the entire coding region. From the cDNA sequence, an open reading frame that encodes sABP as a 704-amino acid protein with molecular mass of 80,800 daltons is predicted. No significant homology was seen between sABP and other proteins in GenBank and NBRF data bases, including the angiotensin-related proteins such as angiotensin converting enzyme, renin, and AT1 angiotensin II receptor. Northern blot analysis of poly(A)+ RNA revealed that the mRNA for sABP is expressed as 5.3- and 2.8-3.2-kilobase transcripts. These transcripts are generated by the use of alternative polyadenylation signals. Within the 3'-untranslated region of the cDNA sequence downstream from the polyadenylation signals for smaller transcripts, a porcine short interspersed repetitive element (SINE) was found; only the longer 5.3-kilobase transcript had the SINE sequence.
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PMID:Molecular cloning of porcine soluble angiotensin-binding protein. 151 39

In isolated rat hepatocytes PMA, angiotensin II and to a lesser extent other hormones induce an early genetic response (increased expression of c-fos, c-mos, c-myc and beta-actin) without altering the expression of the glyceraldehyde 3-phosphate dehydrogenase gene. PMA, PDB and O-met-PMA, but not alpha-phorbol, stimulated c-fos expression. The effect of angiotensin II was inhibited by the AT1 antagonist, Losartan (DuP 753) (Ki approx. 25 nM), but not by the AT2 antagonist PD123177. Angiotensin II was much more effective than vasopressin or epinephrine in inducing proto-oncogene expression which suggests that angiotensin II receptors may exert actions in addition to those shared with the receptors for the other calcium-mobilizing hormones. The effect of PMA and angiotensin II on c-fos expression took place rapidly, with half times of 7 and 12 min, respectively. Actinomycin D markedly diminished basal c-fos expression whereas cycloheximide had the opposite effect. Actinomycin D diminished the effect of PMA and angiotensin II but it did not block them. PMA and the calcium-mobilizing hormones increased c-fos expression above the level observed with cycloheximide alone. These data suggest that PMA and the calcium-mobilizing hormones increased both transcription of the c-fos gene and stabilization of the proto-oncogene mRNA.
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PMID:Angiotensin II and active phorbol esters induce proto-oncogene expression in isolated rat hepatocytes. 152 Jul 5

Angiotensin II (Ang II) given centrally produces an increase in blood pressure and motivation to drink. The physiological mechanisms that mediate the pressor response include release of vasopressin (AVP) and activation of the sympathetic nervous system. Using 2 new Ang II receptor antagonists, we were able to investigate the role of AT1 or AT2 receptors in mediating these effects. Adult male Sprague-Dawley rats were cannulated in the lateral ventricle and 5 days later catheterized in the carotid artery for blood pressure measurements. All experiments were carried out in conscious rats. Three treatments were given intraventricularly (i.v.t.), in 2 microliters artificial cerebrospinal fluid (ACSF) at 30 min intervals: (1) 50 ng Ang II, (2) 0.7 micrograms AT1 antagonist Losartan or 7.0 micrograms AT2 antagonist PD123177, followed by 50 ng Ang II, and (3) 50 ng Ang II, to test for recovery. Blood pressure and drinking measurements were recorded. Also, blood samples for assay of AVP were drawn at 1 or 3 min post-injection in 2 separate groups of rats. We found that both Losartan and PD123177 significantly reduced release of AVP to Ang II 1 min post-injection. Losartan significantly blocked the pressor response (P less than 0.001), while PD123177 had no significant effect. Drinking was also antagonized by Losartan (P less than 0.05) and reduced (n.s.) by PD123177. The results suggest that the pressor response to Ang II (i.v.t.) is predominantly AT1 mediated, while the drinking and AVP responses may be mediated by both receptor subtypes.
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PMID:The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin. 152 Nov 62

The octapeptide, angiotensin II (Ang II), the biologically active component of the renin-angiotensin system, elicits its multiple actions through the stimulation of specific surface receptors on various target organs. Although the existence of Ang II receptor subtypes has been suspected for some time, definitive evidence for Ang II receptor heterogeneity has been obtained only with the recently introduced nonpeptide Ang II receptor antagonists, exemplified by the prototypic compounds DuP 753 and PD 123177. The sites having high affinity for DuP 753 are designated as site 1 (AT1 receptors) and those having a high affinity for PD 123177 as site 2 (AT2 receptors). Unlike Ang I, Ang II, Ang III, and peptide antagonists, such as saralasin, which all are relatively nonselective ligands for both Ang II receptors, the peptides CGP42112A and p-aminophenylalanine6-Ang II show a marked preference for the AT2 site. The occurrence of the AT1 and AT2 receptor subtypes/binding sites identified so far appears widespread. The presence and proportion of these receptors vary significantly among different tissues/organs of the same species and within the same tissue/organ of different species. Despite the abundance of the AT2 site, its functional correlates remain to be determined. The DuP 753-sensitive site (AT1 receptor) mediates all the major Ang II-induced biological effects, including adrenal aldosterone and catecholamine secretion, release of catecholamines from sympathetic ganglia, central nervous system responses, and vasoconstriction.
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PMID:Angiotensin II receptor subtypes. 152 67

Administration of the pyrrolizidine alkaloid monocrotaline (MCT) to rats results in hypertensive pulmonary vascular disease characterized by a structurally based increase in pulmonary vascular resistance and right ventricular hypertrophy. Alterations in lung angiotensin converting enzyme activity in MCT-treated rats have suggested a role for angiotensin II (AII) in the pathogenesis of this model of hypertensive pulmonary vascular disease. To determine if increases in AII contribute to the development of pulmonary hypertension in MCT-treated rats, we examined the effect of chronic administration of the nonpeptide AII receptor antagonist Losartan on indices of pulmonary hypertension, Losartan (DuP 753; 10 mg/kg s.c.) administration for 21 days did not prevent the development of hypertensive pulmonary vascular disease in MCT-treated rats. However, 18 hr after the last dose of Losartan, AII (0.1 micrograms/kg i.v.)-induced pressor responses were inhibited by 63% in Losartan-treated rats. Losartan administration in MCT-treated rats did not prevent increases in pulmonary artery pressure or development of right ventricular hypertrophy. Additionally, increases in medial arterial thickness in pulmonary artery vessels (less than 50 microns and 50-100 microns external diameter) from MCT-treated rats were still evident in Losartan-treated rats. However, Losartan administration decreased medial pulmonary artery thickness of 50 to 100 microns external diameter vessels in control rats. These results demonstrate that AII. acting at the AT1 receptor subtype, does not contribute to pulmonary hypertension in this animal model.
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PMID:Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist. 152 21


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