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

The imino proton resonances of gamma OR3 17mer in water were observed at 500 MHz with the time-shared Redfield pulse train. All of the 17 imino proton resonances could be assigned specifically to individual base pairs by utilizing the trace of NOE connectivities between the imino and adenine C2H protons and between imino protons themselves. AT1 and 17 showed abnormally high chemical shifts in comparison with the other AT pairs. On raising the temperature, broadening of the signal occurred in a sequential manner from the terminals except for AT10 and AT11, which were broadened at a lower temperature than GC12. The relaxation rates of the imino protons were measured by the inversion recovery method. The rates at higher temperatures represent the exchange rates of the imino protons. From the temperature dependences, activation energies of about 15 kcal/mol for the AT imino protons and 23-26 kcal/mol for the GC imino protons were obtained.
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PMID:Dynamic behavior of the imino protons of the gamma OR3 17mer in H2O solution studied by high-resolution NMR. 300 47

Recently, Volk, Geiger, and Raz (Cancer Res., 44: 811-824, 1984) addressed the question of whether variations in actin organization in clones of the murine K-1735 melanoma tumor correlated with their metastatic capability. Using immunofluorescence techniques, they found that clones which had a more ordered actin network were less metastatic, whereas clones having a diffuse actin staining pattern were more metastatic. Similarly, we have found that in the Dunning rat R3327 prostatic adenocarcinoma tumor system, the non-metastatic (less than 0.1%) H-prostatic tumor cell line has a prominent network of actin filament bundles, whereas the highly metastatic (greater than 90%) MatLyLu cell line has a diffuse actin staining pattern. In the low-metastatic (less than 10%) AT1 cell line an intermediate actin organization between H and MatLyLu was observed. Analysis of cell extracts from H- and MatLyLu-cells revealed differences in the level of activity of cellular proteins which affect actin filament assembly and structure in a manner similar to that of the cytochalasins, fungal metabolites which bind with high affinity to the fast-growing end of actin filaments. Extracts of MatLyLu were significantly more effective than those of H-cells in decreasing the extent of actin filament network formation and in inhibiting the rate of filament assembly by blocking monomer addition onto the fast-growing end. Measurements of spin-lattice nuclear magnetic resonance water proton relaxation times (T1) were made in surgically removed tumor tissue from four sublines (H, AT1, MatLyLu, and MatLu) of the Dunning R3327 tumor system. The highly metastatic cell lines had significantly longer water proton T1 relaxation times than did the lines with low metastatic potential. These differences in T1 may reflect the observed alterations in organization of actin filaments within these various sublines of the Dunning R3327 prostatic adenocarcinoma tumor system.
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PMID:Actin filament organization of the Dunning R3327 rat prostatic adenocarcinoma system: correlation with metastatic potential. 394 Jun 53

The pathogenesis of the immunoglobulin deficiency of 20 patients with ataxia telangiectasia was studied using an in vitro immunoglobulin biosynthesis system. 10 patients had no detectable IgA in their serum as assessed by radial diffusion in agar and 3 had a reduced serum IgA concentration. The peripheral blood mononuclear cells of 17 of the patients and 17 normal controls were cultured with pokeweed mitogen for 12 d and the immunoglobulin in the supernatants measured. The immunoglobulin synthesis was below the lower limit of the normal 95% confidence interval for IgM in 5 patients, for IgG in 8, and for IgA in 14. The mononuclear cells from 9 of the 10 patients with a serum IgA concentration less than 0.1 mg/ml failed to synthesize IgA in vitro. None of the patients manifested excessive suppressor cell activity. All patients had reduced but measurable helper T cell activity for immunoglobulin synthesis by co-cultured normal pokeweed mitogen-stimulated B cells (geometric mean 22% of normal). Furthermore, the addition of normal irradiated T cells to patient peripheral blood mononuclear cells led to an augmentation of IgM synthesis in 15 of 17 and to increased IgG synthesis in 9 of the 17 patients studied, including 9 of the 12 patients who had synthesized IgG before the addition of the irradiated T cells. In addition, IgA synthesis was increased in all eight patients examined that had serum IgA concentrations greater than 0.1 mg/ml. These studies suggest that a helper T cell defect contributes to the diminished immunoglobulin synthesis. However, a helper T cell defect does not appear to be the sole cause since there was no IgA synthesis by the peripheral blood mononuclear cells of 9 of the 10 patients with a profoundly reduced serum IgA even when co-cultured with normal T cells. Furthermore, the cells of the nine patients with profoundly reduced IgA levels examined also failed to produce IgA when stimulated with the relatively helper T cell-independent polyclonal activators, Nocardia water soluble mitogen or Epstein-Barr virus. Taken together these data support the view that the reduced immunoglobulin synthesis of these patients is due to defects of both B cells and helper T cells. Such a broad defect in lymphocyte maturation taken in conjunction with our demonstration of persistent alpha fetoprotein production by ataxia telangiectasia patients provides support for the proposal that these patients exhibit a generalized defect in tissue differentiation.
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PMID:Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia. 682 65

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

LR-B/081, methyl-2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl] methyl]-1(6H)-pyrimidinyl] methyl]-3-thiophenecarboxylate, is a recently developed nonpeptide antagonist selective for angiotensin AT1 receptors. The drug has been reported to be an insurmountable angiotensin AT1 receptor antagonist endowed with long-lasting antihypertensive activity. A large body of evidence indicates that angiotensin AT1 receptors mediate the dipsogenic action of angiotensin II in the central nervous system. The present study evaluated the ability of LR-B/081, in comparison with losartan and with its active metabolite EXP3174, to inhibit drinking induced by central injection of angiotensin II in water-sated rats. LR-B/081, in the dose range of 10-1000 pmol/rat, dose dependently inhibited the drinking response to angiotensin II, 10 pmol/rat. The ID50 of LR-B/081 was 25.9 pmol/rat, while that of losartan and EXP3174 was 357 and 3.9 pmol/rat, respectively. Therefore LR-B/081 was about 7 times less potent than EXP3174, but about 14 times more potent than the parent molecule losartan. LR-B/081 altered neither carbachol-induced water intake, nor 15% fat milk intake in rats, suggesting that its effect on angiotensin II-induced drinking is a behaviourally selective effect. These findings show that LR-B/081 potently inhibits central angiotensin AT1 receptors involved in behaviourally selective effect. These findings show that LR-B/081 potently inhibits central angiotensin AT1 receptors involved in the control of body fluid homeostasis and suggest that this drug might be an interesting pharmacological tool to further investigate the role of the central renin-angiotensin system in physiological or pathological conditions.
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PMID:The selective angiotensin AT1 receptor antagonist LR-B/081 potently inhibits drinking induced by central injection of angiotensin II in rats. 749 12

Fructose feeding induces a moderate increase in blood pressure levels in normal rats that is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore the mechanisms underlying fructose-induced hypertension, the effects of the AT1 receptor antagonist losartan on blood pressure, insulin resistance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch (control), and half of each group received losartan (1 mg/kg per day) in the drinking water. Fructose-fed rats showed higher (P < .05) blood pressure levels and plasma concentrations of triglycerides and insulin than those of controls. Losartan treatment prevented both blood pressure elevation and hyperinsulinemia in fructose-fed rats but not elevation of plasma triglycerides. Plasma glucose and insulin levels in response to an oral glucose load were higher (P < .05) in fructose-fed rats than in controls. These exaggerated responses were prevented by losartan treatment. No differences in the constrictor responses of mesenteric vascular beds to KCl (60 mumol), angiotensin II (1 nmol), phenylephrine (10(-5) mol/L), or endothelin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontracted mesenteric vascular beds and constrictor response to the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (100 nmol) were comparable in both groups. Losartan blunted angiotensin II constriction and reduced (P < .05) responses to phenylephrine in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of losartan on blood pressure, metabolic alterations, and vascular reactivity in the fructose-induced hypertensive rat. 749 71

[3H]Senktide, a highly selective tachykinin NK3 receptor agonist, was used to study tachykinin NK3 receptors of rat and guinea pig brain. Guinea pig brain membranes had a Kd of 3.9 +/- 0.5 nM and a Bmax of 42 fmol/mg. Dose-displacement experiments with neurokinins and selective tachykinin receptor agonists revealed the following order of potency: [MePhe7]neurokinin B > neurokinin B > substance P > neurokinin A. This order is typical for a tachykinin NK3 receptor. To further characterize the specificity of this receptor, the effects of unrelated compounds such as: bradykinin, angiotensin II, bombesin and their structural analogs were also evaluated on the binding of [3H]senktide. Unexpectedly, the angiotensin AT1 receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole potassium salt), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl) methyl]-3H-imidazo[4,5-beta]pyridine H2O) and EXP 3174 (2-n-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]i midazole- 5-carboxylic acid), inhibited the binding of [3H]senktide to its receptor in the guinea pig brain membranes with IC50 values of 18 microM, 25 microM and 50 microM, respectively. Similar effects were also observed with rat brain membranes. Angiotensin II, saralasin ([Sar1,Val5,Ala8]angiotensin II, a peptide angiotensin AT1 receptor antagonist) and PD 123,319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)-4,5, 6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, a known non-peptide angiotensin AT2 receptor antagonist) did not inhibit the binding of [3H]senktide to either type of membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-peptide angiotensin receptor antagonists bind to tachykinin NK3 receptors of rat and guinea pig brain. 751 91

1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significantly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain. However,the cardiovascular and behavioural responses induced by central tachykinin agonists (SP, NKA and[MePhe7]NKB) and All are mediated by unrelated mechanisms.
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PMID:Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat. 754 Dec 80

We have characterized a specific binding site for angiotensin IV in bovine adrenal cortex membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.24 +/- 0.03 nM). The binding site is saturable and relatively abundant (maximal binding capacity around 0.5 pmol/mg protein). Non-equilibrium kinetic analyses at 37 degrees C revealed a calculated kinetic Kd of 47 pM. The binding site is pharmacologically distinct from the classic angiotensin receptors AT1 or AT2. Competitive binding studies with bovine adrenal cortex membranes demonstrated the following rank order of effectiveness: angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) = angiotensin II-(3-7) (Val-Tyr-Ile-His-Pro) > angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) > or = angiotensin II-(4-7) (Tyr-Ile-His-Pro) > angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) > angiotensin II-(1-6) (Asp-Arg-Val-Tyr-Ile-His) > angiotensin II-(4-8) (Tyr-Ile-His-Pro-Phe) > > > angiotensin II-(3-6) (Val-Tyr-Ile-His), angiotensin II-(4-6) (Tyr-Ile-His), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'(1-H-tetrazol-5-yl)[1,1'-biphenyl]-4-y l) methyl]-3-H-imidazo[4,5-beta]pyridine H2O) and PD 123319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)4,5,6 ,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid). The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensioffn IV to bovine adrenal cortex membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A specific binding site recognizing a fragment of angiotensin II in bovine adrenal cortex membranes. 769 12

Antisense oligodeoxynucleotides (AS-ODN) to AT1 receptor mRNA inhibit high blood pressure in Spontaneously Hypertensive Rats (SHR) when injected into the brain. The effect is presumably through inhibition of the actions of brain angiotensin II (Ang II). Central injection of Ang II elicits several physiological responses including release of vasopressin and motivation to drink. The angiotensin II type-I (AT1) receptor is located in brain regions which have been implicated in mediating these effects. Therefore we hypothesized that AS-ODN to AT1 mRNA would inhibit the drinking and AVP response to central administration of Ang II in adult male SHR. AS-ODN were constructed to bases +63 to +77 (15-mer) of the AT1 receptor RNA. 24 h after AS-ODN treatment (50 micrograms/4 microliters) (intracerebroventricularly, i.c.v.), the drinking response to Ang II (50 ng, i.c.v.) was significantly reduced in the SHR (P < 0.05). The drinking response to Ang II (i.c.v.) was also reduced in the Sprague-Dawley rats (P < 0.05). There was no reduction of water intake in the control animals treated with scrambled ODN (SC-ODN). Repeated injection of AS-ODN did not produce a greater reduction in drinking response. Arginine vasopressin (AVP) release to central Ang II was significantly decreased after AS-ODN treatment when compared to vehicle (P < 0.05) and to SC-ODN injections (P < 0.05). Radioligand binding assays of the hypothalamic block after AS-ODN treatment showed a significant decrease of AT1 receptor binding (P < 0.05). The results show that the antisense inhibition of brain AT1 receptor gene expression decreases the Ang II induced drinking and AVP release responses.
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PMID:Antisense oligonucleotide to AT1 receptor mRNA inhibits central angiotensin induced thirst and vasopressin. 771 85


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