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)

When treated at pH less than 4.5, yeast nuclei or chromatin lose endogenous RNA synthetic activity. This activity is regained by addition of exogenous RNA polymerases. The specificity of transcription in this system by homologous RNA polymerases I and III has been investigated by gel electrophoresis, hybridization analysis, and RNase T1 mapping. Exogenous RNA polymerase I selectively transcribes rRNA genes. The transcription of these genes by polymerase I is 30- and 8-fold more selective than RNA polymerase III and Escherichia coli polymerase holoenzyme, respectively. Exogenous RNA polymerase III synthesized RNAs similar in size to authentic 5 S RNA, 4.5 S pre-tRNA, and 4 S tRNA. Eleven per cent of this RNA is 5 S RNA as determined by hybridization. Neither polymerase I nor E. coli polymerase synthesizes detectable quantities of RNA in this size range. AT1 ribonuclease digestion of 5 S RNA synthesized by exogenous RNA polymerase III acting on acid-treated chromatin gives a fragment pattern corresponding to that of 5 S RNA. Thus, RNA polymerase III transcribes the entire 5 S gene in this system.
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PMID:Specific gene transcription in yeast nuclei and chromatin by added homologous RNA polymerases I and II. 36 64

Angiotensin II (Ang II) receptor subtypes in the rat kidney were investigated by using type 1 (AT1) and type 2 (AT2) Ang II receptor antagonists to discriminate specific 125I-[Sar1,Ile8] Ang II binding sites with in vitro autoradiography. DuP 753, a nonpeptide Ang II antagonist specific for the AT1 sites, potently displaced binding in glomeruli (Ki = 23.9 +/- 3.3 nM) and proximal tubules (Ki = 43.4 +/- 17 nM). By contrast, the AT2 antagonists, PD 123177 and CGP 42112A, were very weak in competing for specific 125I-[Sar1,Ile8] Ang II binding sites. AT1 receptors, as determined in the presence of an excess concentration (10 microM) of the AT2 antagonist, PD 123177, account for 95% of total renal Ang II receptors, whereas AT2 receptors, as determined in the presence of an excess concentration (10 microM) of the AT1 antagonist, DuP 753, represent approximately 5% of total renal Ang II receptors. In addition, the reducing agent, dithiothreitol, produces a dose-dependent inhibition of Ang II receptor binding with an IC50 of 2 mM, a characteristic of the AT1 receptors. These findings indicate that the AT1 receptor is the predominant subtype at multiple anatomical sites in the rat kidney.
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PMID:In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney. 127 63

The present study demonstrates the existence and regional distribution of angiotensin II AT1 receptor subtype mRNA expression in the rat brain by the use of in situ hybridization and RNase protection assay. Substantial expression levels in the brain have only been detected in certain distinct areas, such as the subfornical organ, the parvocellular part of the paraventricular hypothalamic nucleus, and the median preoptic nucleus. The results give further evidence for the involvement of the angiotensin II AT1 receptor subtype in the classical functions of central angiotensin II, like blood pressure control, body fluid homeostasis and in corticotropin-releasing factor (CRF) secretion.
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PMID:The distribution of angiotensin II AT1 receptor subtype mRNA in the rat brain. 128 Jul 91

Angiotensin II (ANG II) is the primary mediator of the renin-angiotensin system, which has an important functional role in cardiovascular homeostasis. The angiotensin receptor and its functional correlates have been redefined by the cloning of angiotensin receptors and the discovery and widespread study of specific nonpeptide ANG II-receptor antagonists losartan (AT1 selective) and PD123177 (AT2 selective). With these antagonists, it has been possible to extend the concept of ANG II-receptor heterogeneity to virtually every tissue and species. The losartan-sensitive sites have been shown to mediate all of the major ANG II-induced biologic effects, including vasoconstriction, aldosterone and catecholamine release, and central, ANG II-induced drinking behavior. The function of the AT2 site is not fully understood, but it may be involved in neuronal ion channel modulation and in fibroblast collagen metabolism. The presence of AT2 sites in fetal tissues and in discrete locations in the brain has encouraged continued research. Losartan, which represents the first of a new class of therapeutic agents, is currently undergoing clinical trials. A growing number of other AT1-selective ANG II-receptor antagonists are under development, including L-158,809, SKF 108566, and GR117285. Rat AT1-receptor subtypes have been cloned and sequenced (AT1A and AT1B). Human ANG II receptors have also been cloned and shown to have high affinity for losartan. A number of atypical angiotensin-binding sites have been identified from mycoplasma, amphibians, and mouse neuroblastoma, which are not sensitive to either losartan or PD123177.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II receptors and functional correlates. 129 Jun 17

Angiotensin II is the principal effector molecule of the renin-angiotensin system. Its effects are mediated by cell surface proteins termed AT receptors. On the basis of radioligand binding studies, these have been pharmacologically subdivided into two classes, termed AT1 receptors and AT2 binding sites (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196-203). AT1 receptors appear to mediate the major cardiovascular effects of angiotensin II, whereas no known physiological properties appear to be coupled to AT2 binding sites (Wong PC, et al, J Pharmacol Exp Ther 1990;255:584-592). To gain further insight into the function of AT1 receptors we have isolated rat cDNA's and genes encoding two distinct but highly similar isoforms of AT1 receptors, termed AT1a and AT1b receptors. Two cDNA's encoding the vascular AT1a receptor were isolated by an expression cloning strategy from a cDNA library prepared from vascular smooth muscle cells. The properties of the clones isolated by this approach are consistent with known pharmacological, biochemical signaling, and tissue distribution properties of AT1 receptors. Using this cDNA as a probe, a second isoform of rat AT1 receptor was isolated from a genomic library. This receptor, termed the AT1b receptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the AT1a receptor. However, the tissue-specific expression pattern of the AT1b gene differs significantly from that for the AT1a receptor.
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PMID:Molecular cloning of AT1 angiotensin receptors. 129 Jun 18

Renin-angiotensin (RA) system plays an important role in cardiovascular homeostasis. Here, we have described the recent progress in our study of renin release as well as the cellular action of angiotensin II. (1) Microdissection of an isolated afferent artery with or without macula densa (MD) has revealed that renin release is regulated by NaCl exposure to MD. Furosemide, prostaglandins (PGE2 and PGI2) and adenosine modulate its function. (2) Angiotensin (ang) II increases cytosolic free calcium and induces the formation of inositolphosphates in vascular smooth muscle cells. Deduced protein structure of ang II receptor (AT1-R) cDNA has indicated the presumed link of AT1-R with phospholipase C. Through the cellular action, ang II has been reported to regulate gene expression.
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PMID:[Mechanism of renin release and cellular action of angiotensin II]. 129 35

A simple technique to isolate rat renal preglomerular vessels is described. Kidneys were pressed against a 0.3 mm stainless steel grid. The whole vascular tree, including the interlobar, arcuate, and interlobular arteries, as well as the afferent arterioles, remained on the grid surface from where they were recovered. Extensive washing yielded a highly pure preparation of renal microvessels. Radioligand binding experiments were performed to characterize 125I-[Sar1,Ile8]-ANG II binding sites in preglomerular microvessel membranes. Equilibrium saturation binding experiments revealed the presence of one group of high affinity receptors (Kd = 1.22 +/- 0.171 nM; Bmax = 209 +/- 14 fmol/mg protein). Competitive inhibition experiments with two highly specific nonpeptide ANG II antagonists, losartan (DuP 753), which is specific for the AT1 receptor subtype, and PD123319, which is specific for the AT2 subtype, demonstrated that the large majority of, if not all, ANG II receptors in rat renal preglomerular vessels correspond to the AT1 subtype.
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PMID:Angiotensin II receptor subtypes in rat renal preglomerular vessels. 129 11

The control of Na+/K+ pump activity was studied in rat adrenal glomerulosa cells. Ninety percent of K+/86Rb accumulation was blocked by ouabain, and the dose-response curve of inhibition by ouabain was monophasic (IC50, approximately 80 microM), suggesting the role of a single type of Na+/K+ pump (alpha-isoenzyme) in 86Rb accumulation by rat glomerulosa cells. The basal activity of the Na+/K+ pump was much higher in glomerulosa cells than in adrenal fasciculata cells or hepatocytes, as judged by the ouabain-sensitive uptake of 86Rb. In contrast to the two other cell types, increasing Na+ influx with the Na+ ionophore monensin failed to significantly affect ouabain-sensitive 86Rb uptake in glomerulosa cells, suggesting that in glomerulosa cells even the resting intracellular Na+ concentration is sufficient for maximal activity of the Na+/K+ pump. Angiotensin-II (AII) inhibited the ouabain-sensitive 86Rb uptake by glomerulosa cells. The effect of AII was abolished by the selective antagonist of the AT1 type of AII receptors (DuP 753), while PD 123177, an AT2 antagonist was ineffective. AT1 receptors of glomerulosa cells coupled to phospholipase-C activation and, thus, to Ca2+ signal. The inhibitory effect of AII was dependent on the extracellular Ca2+ concentration, but an elevation of cytoplasmic Ca2+ by Ca2+ ionophore ionomycin failed to mimic the effect of AII. These data suggest that Ca2+ is required for but does not mediate the inhibitory effect of AII on the Na+/K+pump. Pharmacological activation of protein kinase-C by phorbol ester did not modify 86Rb accumulation by the cells. Ouabain induced a nifedipine-sensitive elevation in the cytoplasmic Ca2+ concentration and exerted a stimulatory effect on aldosterone production, suggesting participation of the inhibition of the Na+/K+ pump in the aldosterone stimulatory action of AII.
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PMID:Angiotensin-II inhibits Na+/K+ pump in rat adrenal glomerulosa cells: possible contribution to stimulation of aldosterone production. 131 Dec 45

Angiotensin II (AngII) elicited a rapid and dose-related production of intracellular cyclic GMP (cGMP) in murine neuroblastoma N1E-115 cells. The agonist-induced rise in cGMP levels was blocked in a monophasic fashion by the AT1-selective antagonist DuP 753 or the nonselective antagonist [Sarc1,Ile8]-AngII, and both antagonists produced complete inhibition of the cGMP response elicited by submaximal concentrations of AngII. In contrast, the AT2-selective antagonist CGP 42112A inhibited the cGMP response biphasically. At lower antagonist concentrations, agonist-induced cGMP production was only partially inhibited, whereas complete inhibition was observed only when the concentration of CGP 42112A was increased sufficiently to interact with both AT1 and AT2 receptor subtypes. AngII also increased inositol trisphosphate (InsP3) levels in N1E-115 cells. However, the InsP3 response was mediated exclusively by the AT1 receptor subtype because it was inhibited by lower, AT1-selective concentrations of DuP 753, whereas only higher, nonselective concentrations of CGP 42112A were effective. Finally, the stimulatory effects of AngII on cGMP production appeared to be mediated by the intracellular formation of nitric oxide in that they were attenuated by the nitric oxide synthase inhibitor, N-monomethyl-L-arginine. Collectively, these results suggest that the AngII-elicited rise in cGMP levels may require an interaction between AT1-mediated mobilization of intracellular Ca2+, as well as some partial role of AT2 receptors.
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PMID:Angiotensin-induced cyclic GMP production is mediated by multiple receptor subtypes and nitric oxide in N1E-115 neuroblastoma cells. 131 56

We studied the effects of the estrous cycle, ovariectomy and estrogen replacement on angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) and angiotensin II (AT) receptors in the pituitary gland of the female rat. Quantitative autoradiography, with the use of consecutive pituitary sections, allowed for simultaneous determination of changes in binding and in the potential AT synthetic ability of individual pituitaries, and for a correlation between these two phenomena. In the anterior pituitary, ACE activity and binding of the ACE inhibitor [125I]-351A were not changed during the estrous cycle. Ovariectomy produced a significant increase in ACE activity and binding, and both of these parameters returned to normal after estrogen replacement. There were no changes in ACE activity or binding in the posterior pituitary during the estrous cycle or after ovariectomy or hormone replacement. AT receptors were characterized as of the AT1 type, since they were displaced by the selective AT1 antagonist DuP 753 and not by the AT2 competitor PD 123177. There were marked changes in the concentration of AT1 receptors during the estrous cycle, with highest numbers in metestrus, lower in estrus and diestrus, and lowest during proestrus. Estrogen replacement in ovariectomized rats decreased AT1 receptor number in the anterior pituitary. Our results indicate a dual effect of estrogen on anterior pituitary AT, physiologically on AT receptor expression and pharmacologically on ACE activity.
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PMID:Estrogens regulate angiotensin-converting enzyme and angiotensin receptors in female rat anterior pituitary. 131 39


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