Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renin-like activity (RLA), angiotensin I converting enzyme-like (ACELA), and kallikrein-like activity (KLA), activities of the key enzymes of renin-angiotensin and kallikrein-kinin systems, were sought in the kidney of the African lungfish Protopterus annectens during the aquatic phase. RLA, examined by RIA (using porcine angiotensinogen as substrate), was 0.38 +/- 0.05 ng angiotensin I/mg protein/hr. ACELA and KLA were investigated in assays spectrophotometrically. ACELA, measured at 37 and at 20 degrees , was, respectively, 1.55 +/- 0.55 and 0.61 +/- 0.23 nmol hippurate/min/mg protein. KLA was 7.34 +/- 0.93 mU/mg protein in the crude kidney extract and 31.05 +/- 7.50 mU/mg protein after electrophoretic purification. Renal kininogenase activity was inhibited by 100% by D-Phe-Phe-Arg-chloromethyl ketone (10 microM), 98% by phenylmethylsulfonyl fluoride (2 nM), and 91% by aprotinin (1000 kIU). The apparent molecular weight of the renal kininogenase on SDS-PAGE was 27,000 Da. Both the renal enzyme and the purified glandular kallikrein, used as a control, have the same mobility on polyacrylamide gel electrophoresis. Immunoreactivities toward angiotensin II and bradykinin were localized by double immunostaining in the same cells of the proximal tubules. Putative angiotensin II receptors were demonstrated immunohistochemically, in the supranuclear region of proximal tubular cells, using an antibody to the sequence between amino acids 225 and 237 of the mammalian AT1 receptor.
Gen Comp Endocrinol 1996 Jul
PMID:The kallikrein-kinin and renin-angiotensin systems in the kidney of an African lungfish, Protopterus annectens. 881 41

1. The effects of angiotensin (Ang) II receptor antagonist, SC-52458, on peak and plateau components of Ang II-induced contraction were evaluated in the guinea-pig taenia coli. 2. SC-52458 suppressed both the components of and increases in cytoplasmic Ca2+ concentrations, [Ca2+]i, coupled with the contraction by Ang II; tetrodotoxin and atropine did not affect the contractions. 3. SC-52458 inhibited a plateau component of the contraction induced by K(+)-depolarization to some extent, without affecting a peak component. 4. SC-52458 suppressed both the contraction and increase of [Ca2+]i by antagonizing AT1 receptors in the smooth muscle.
Gen Pharmacol 1996 Oct
PMID:Effects of SC-52458, a new nonpeptide angiotensin II receptor antagonist, on increase in cytoplasmic Ca2+ concentrations and contraction induced by angiotensin II and K(+)-depolarization in guinea-pig taenia coli. 898 Oct 65

The presence of specific Ang II receptors in membrane fractions was investigated using 125I-labeled homologous Ang II ([Asn1, Pro3, Ile5]Ang II; df Ang II) in Triakis scyllia. Specific binding sites occurred in a variety of tissues, with highest binding in interrenal tissue (17.11 +/- 2.45 fmol Ang II/mg protein) and gill (6.26 +/- 0. 69 fmol Ang II/mg protein) and possible Ang II receptors in rectal gland and other tissues. 125I-[Asn1, Pro3, Ile5]Ang II (10(-10)M) binding to branchial cell membrane fraction (25 microg protein) in 5 mM MgCl2, 125 mM NaCl, 50 mM Tris-HCl, 0.2% bovine serum albumin at 28 degrees (1) is rapid and saturable; (2) increases as a function of membrane concentration and time; and (3) optimally fits to a two-site (high-and low-affinity) model. The equilibrium dissociation constant (0.11 +/- 0.01 nM) and binding site concentration (35.00 +/- 1.16 fmol/mg protein) are similar to those of mammalian and avian vascular Ang II receptors. Bound labeled ligand was not competitively displaced by dogfish Ang I, dogfish C-type natriuretic peptide, bradykinin, or the AT1 receptor antagonist, CV 11974. The AT2 receptor antagonist, CGP 42112, was much less potent at displacing the labeled ligand compared to the unlabeled ligand.
Gen Comp Endocrinol 1997 Jan
PMID:The presence of angiotensin II receptors in elasmobranchs. 900 Apr 63

Mutation of the essential Schizosaccharomyces pombe rad4/cut5 gene causes sensitivity to UV and ionising radiation at the permissive temperature whilst at the restrictive temperature cells fail to undergo DNA replication but still attempt mitosis owing to a defective S-phase checkpoint response. Many mutations in genes encoding DNA replication proteins also abolish checkpoint responses, possibly because the replication machinery is a pre-requisite for the generation of the signal. We demonstrate here that rad4/cut5 cells fail to arrest cell division when treated with the replication inhibitor hydroxyurea at the semi-permissive temperature 32 degrees C, but retain essentially normal replicative capacity. This demonstrates that the replication and checkpoint function of the rad4/cut5 gene product can be separated and that the Rad4 protein differs from other replication proteins in being directly involved in generating the S-phase checkpoint signal. Furthermore, we have investigated the checkpoint response or rad4/cut5-deficient cells to gamma-irradiation and UV-mimetic drugs. We find that, at the restrictive temperature, the rad4-/cut5- cells fail to delay mitosis in response to gamma-irradiation whilst retaining a normal checkpoint response to the UV-mimetic drug 4-nitroquinoline-1-oxide. The lack of the gamma-irradiation checkpoint is reminiscent of the deficiency associated with mutation of the human ATM locus, the causative deficiency of the heritable disorder ataxia telangiectasia. The implications of our results for the organisation of distinct checkpoint-response pathways in both fission yeast and mammalian cells are discussed. Moreover the data are consistent with a model in which the generation of the S-Phase checkpoint signal is DNA polymerase epsilon dependent.
Mol Gen Genet 1997 Jul
PMID:Characterisation of the Schizosaccharomyces pombe rad4/cut5 mutant phenotypes: dissection of DNA replication and G2 checkpoint control function. 926 24

1. Angiotensin II (Ang II), the main effector of the renin-angiotensin system, exerts its vasoconstrictory and trophic actions on smooth muscle cells via AT1 receptors. However, Ang II does not act only on smooth muscle cells, as Ang II receptors are also present in endothelial cells. 2. The receptor type on these cells differs depending on the origin of the endothelium and the species. The rat endothelial receptors are mostly of the AT1 type, but AT2 receptors have also been found. The pharmacological characteristics of the AT1 receptors on endothelial cells are similar to those of other cell types. 3. Ang II stimulates phospholipase C and phospholipase A2 activation via the AT1 receptor in endothelial cells. Ang II also stimulates the tyrosine phosphorylation of several proteins in these cells. 4. Some studies suggest that the AT1 receptor mediates the release of vasodilator molecules by endothelial cells and could modulate Ang II effect on smooth muscle cells. Ang II may also inhibit endothelial cell growth via the AT2 receptor. Finally, endothelial Ang II receptors may be implicated in the regulation of fibrinolysis.
Gen Pharmacol 1997 Nov
PMID:Angiotensin II receptors in endothelial cells. 934 11

1. Angiotensin II (ang II) produced significant (P<0.01) increases of inositol 1,4,5-mono-, -di- and -triphosphates (IP1, IP2 and IP3) within 1 min of treatment of cardiomyocytes prepared as primary culture from 7-day-old chick embryo hearts. 2. The ang II receptor type 1 (AT1-R) antagonist losartan blocked ang II-stimulated production of IP3; however, the inhibition was not complete even at 10(-5) M. 3. The ang II receptor type 2 (AT2-R) antagonist PD123319 blocked ang II-induced IP3 production but to a lesser extent than losartan. At 10(-5) M, losartan reduced ang II-induced formation of IP3 by 71%, whereas PD123319 reduced IP3 formation by ang II by 40%. 4. Neither losartan nor PD123319, 10(-5) M, affected IP3 formation in cardiomyocytes that were not treated by ang II. 5. The combination of both antagonists, at concentrations that each partly reduced IP3, completely inhibited IP3 formation. Thus AT1 and AT2 receptor blockade may be necessary to completely block the effects of ang II mediated by the IP3 signal transduction pathway.
Gen Pharmacol 1998 Mar
PMID:Comparison of angiotensin II type-1 and type-2 receptor antagonists on angiotensin II-induced IP3 generation in cardiomyocytes. 951 88

Glomeruli were isolated from the kidney of freshwater-adapted rainbow trout, Oncorhynchus mykiss, to qualitatively evaluate changes in cellular calcium associated with angiotensin II ([Asn1Val5]-Ang II) receptor stimulation and antagonism by the Ang II receptor antagonist losartan. Microspectrofluorometry using the fluorescent calcium indicator dye Calcium Green recorded fluorescence changes in isolated single glomeruli. Isolated glomeruli containing ester-loaded Calcium Green showed an Ang-II-induced transient rise in fluorescence. This transient rise showed an increased peak amplitude with increased Ang II concentration (10(-9) to 10(-6) M), but only a very small response was detectable in glomeruli exposed to 10(-9) M Ang II. The biphenylimidazole compound losartan (=DuP 753), an antagonist of the mammalian AT1 subtype Ang II receptor, initiated a transient agonistic rise in glomerular fluorescence at high concentration (10(-5), 10(-4), and 10(-3) M). However, the responses to 10(-6) 10(-7) M losartan were small or very low in each case. Losartan (10(-4) or 10(-7) M) antagonised the Ang-II-induced signalling in isolated glomeruli exposed to 10(-7) or 10(-6) M Ang II, respectively. This is the first evidence for functional AT1-like Ang II receptors coupled to cellular calcium signalling in the glomeruli of rainbow trout.
Gen Comp Endocrinol 1999 Feb
PMID:Angiotensin II-induced calcium signalling in isolated glomeruli from fish kidney (Oncorhynchus mykiss) and effects of losartan. 1008 34

An ATM-like gene was identified in the genome of Caenorhabditis elegans. The putative product of the gene, termed Ce-atl-1 (C. elegans ATM-like 1) consists of 2514 amino acid residues. The C-terminal sequence, which contains a PI-3 kinase-like domain, showed good homology with the products of the gene MEC1/ESR1 from budding yeast, the rad3+ gene of fission yeast and mammalian ATM (ataxia-telangiectasia and rad3+ related) genes. The results of RNA-mediated interference indicated that the major phenotype associated with repression of Ce-atl-1 was lethality (approximately 50-80%) during early embryogenesis. Among the surviving progeny, males (XO animals) arose at a high frequency (2-30%). In addition, 5% of oocyte chromosomes demonstrated aneuploidy due to a defect in pre-meiotic chromosomal segregation. Gene expression analyses indicated that Ce-atl-1 mRNA was expressed in all larval stages and that its level increased about fivefold in the adult stage. The adult expression level was decreased in the glp-4 mutant, which is defective in germ line proliferation. Ce-atl-1 was strongly expressed in both the mitotic and meiotic cells of adult gonads. In summary, Ce-atl-1 appears to be important for early embryogenesis, and loss of its function results in a defect in chromosome segregation, similar to what has been observed for AT-related proteins.
Mol Gen Genet 2000 Sep
PMID:Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis elegans. 1101 41

In the present study the gene expression of components of the renin-angiotensin system was investigated in fat tissue of rats. mRNAs for angiotensinogen, renin, angiotensin-converting enzyme and type I (AT1) angiotensin II receptor were detected in the stromal-vascular fraction of the fat tissue and the same mRNAs, with the exception of the angiotesin-converting enzyme, in the adipocyte fraction. Renin and angiotensin-converting enzyme activity was measured. The main source of renin activity was found in adipocytes and some minor activity in the stromal-vascular fraction, while the majority of the angiotensin-converting enzyme activity was in the stromal-vascular fraction. The present data provide evidence for the presence of the active renin-angiotensin system in rat adipose tissue.
Gen Physiol Biophys 2000 Sep
PMID:Rat epididymal fat tissue express all components of the renin-angiotensin system. 1131 63

Dorsal aortic blood flow (DABF) and caudal venous blood flow (CVBF) were measured in free-swimming conscious freshwater (FW) North American eels (Anguilla rostrata) with Doppler-flow probes. DABF and CVBF increased in a dose-dependent manner following iv doses of [Asn(1), Val(5), Gly(9)]-angiotensin I (ANG I), [Asn(1), Val(5)]-angiotensin II (ANG II), and [Val(4)]-angiotensin III (ANG III) ranging from 5 to 50 ng x kg bw(-1). A minimum effective dose for ANG I and ANG II was 5 ng x kg bw(-1); that for ANG III was 10 ng x kg bw(-1). DABF and CVBF rates increased during the first 2 min and remained elevated for 20-50 min. Flow responses similar to those of ANG II in form and magnitude followed iv injections of extracts of corpuscles of Stannius (CS-EXT). Increases in DABF and CVBF following injections of ANG I, human renin substrate (hRS), and CS-EXT were all blocked by the angiotensin-converting enzyme inhibitor Captopril. Increases in DABF and CVBF which followed injections of hRS and CS-EXT were blocked completely by pepstatin A. [Sar(1), Val(5)]-ANG II (Sarile) blocked completely the DABF and CVBF responses to ANG II and CS-EXT, but the mammalian receptor antagonists losartan (AT1) and PD123319 (AT2) only partially blocked them. These findings support strongly the hypothesis that the corpuscles of Stannius secrete renin or isorenin and that the renin-angiotensin system regulates cardiovascular function in freshwater eels and other bony fishes that possess them.
Gen Comp Endocrinol 2001 Nov
PMID:Corpuscles of Stannius secrete renin or an isorenin that regulates cardiovascular function in freshwater North American eels, Anguilla rostrata LeSueur. 1170 85


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