Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The active sites of 3 types of aspartic proteases are modeled, based on crystallographic coordinates of endothiapepsin and of a model of HIV-1 protease. The enthalpies of deprotonation from neutral to mono-anion and to dianion are calculated with semiempirical minimal neglect of differential overlap, hydrogen bonding corrected (MNDO/H). This quantum mechanical study of models for the active sites of pepsins, human renin and retroviral aspartic proteases demonstrates that the replacements of Thr-218 from pepsins by Ala in human renin and of both Ser-35 and Thr-218 by alanines in retroviral proteases increases the proton affinity and modulates the charge distribution of those active sites compared to the pepsins.
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PMID:Modulation of the affinity of aspartic proteases by the mutated residues in active site models. 210 98

Twenty-seven children [2 with chronic renal failure (CRF)] with reflux or obstructive nephropathy underwent intravenous urography with iopamidol 370, a nonionic contrast medium 1 (CM), osmolality 796 mosmol/kg, for renal growth evaluation. Mean iopamidol dosing was 1.69 ml/kg (range 1.22-2.42); the 2 children with CRF received 2 and 2.42 ml/kg respectively. One hour after infusion a significant decrease in haematocrit, haemoglobin, plasma sodium (Na+), chloride (Cl-), renin activity and aldosterone was observed, consistent with a possible plasma volume expansion due to the slightly hypertonic CM. At the same time there was a significant increase in fractional excretion of Na+, Cl- and potassium, probably due to the haemodynamic effects and tubular response to a substance acting as on osmotic diuretic. The -24 to +48 h monitoring of albuminuria, beta-2-microglobulin excretion, and in 4 children excretion of N-acetyl-beta-glucosaminidase and alanine-aminopeptidase did not show any relevant nephrotoxicity. No untoward effect of clinical relevance was observed.
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PMID:Intravenous urography with iopamidol in children with reflux and obstructive nephropathy: effects on glomerular and tubular functions and the renin-angiotensin-aldosterone system. 220 71

A new potent renin inhibitor, Iva-Phe-Nle-Sta-Ala-Sta-OH (SR 42128), and its arginine salt (SR 42128A) have been synthesized. This compound had a concentration required to displace 50% of ligand binding of 2.8 X 10(-8) M toward human plasma renin at pH 7.4 and was 2,000 times more potent than pepstatin. All primate renins tested were inhibited within the same order of magnitude whereas other animal renins were much less inhibited. The effect in vivo of SR 42128A was studied in sodium-depleted conscious monkeys. A single dose of SR 42128A produced a dose-dependent blood pressure decrease as well as a dose-dependent inhibition of plasma renin activity (PRA). Blood pressure was still significantly lowered 3 h after a single administration of 3 or 10 mg/kg whereas PRA was still completely inhibited. SR 42128 is a potent and long-acting tool for studying the role of the renin angiotensin system in primates and humans.
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PMID:In vitro and in vivo inhibition of human and primate renin by a new potent renin inhibitor: SR 42128. 241 15

The primary structure of human renin, recently established from the complementary DNA sequence of its messenger RNA, shows a strong homology to other aspartyl proteases. This homology has permitted the construction of a model of the three-dimensional structure of renin based on the crystallographically determined structures of three aspartyl proteases: penicillopepsin, endothiapepsin, and rhizopuspepsin. Using an algorithm in which a spherical probe approximating the size of the antibody-binding domain (1-nm radius) was allowed to contact the surface of the renin model, we predicted 12 to 15 peptides to be immunogenic epitopes. We synthesized peptides corresponding to three different regions of the model: Cys-Gly-Ser-Asp-Pro-Gln-His-Tyr-Glu-Gly-amide (C-180-188), Tyr-Leu-Leu-Cys-Glu-Asp-Gly-Cys-Leu-Ala-Leu-amide (Y-215-224; disulfide bond between cysteines) and Tyr-Gly-Ser-Ser-Thr-Leu-Leu-Cys-Glu-Asp-Gly-Cys-Leu-Ala-Leu-amide (Y-211-224; disulfide bond between cysteines), and Cys-Tyr-Ser-Ser-Lys-Lys-Leu-Cys-Gly (C-290-296-G; disulfide bond between cysteines). All four peptides were tested for their binding to 11 polyclonal and 7 monoclonal antibodies raised against pure human renin, in both a solution assay and an enzyme-linked immunosorbent assay. Peptides Y-215-224 and Y-211-224 bound to all 11 polyclonal antibodies in the solution assay, and peptide Y211-224 bound to eight of them in the enzyme-linked immunosorbent assay. Therefore, region 211-224 can be identified as a major epitope of the human renin molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study of the antigenic determinants of human renin. 242 34

A novel tripeptidic renin inhibitor is described, SQ 32,970, that will potently inhibit endothia protease. This inhibitor can be coupled to Sepharose and will allow the affinity-purification of endothia protease in one step to greater than 95% purity as measured by SDS PAGE. The purified endothia protease cleaves the Lys-Pro-Ala-Glu-Phe-Nph-Arg-Leu substrate at the Phe-Nph bond with a Kcat/Km of 7445 (s-1 mM-1) at pH 3.1 and 4057 (s-1 mM-1) at pH 6.0. Affinity purified endothia protease can be crystallized in the pH range in which it is enzymatically active and can be inhibited by renin inhibitors.
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PMID:Affinity purification of endothia protease with a novel renin inhibitor SQ 32,970. 265 96

We investigated the relation of calcitonin as a calcium-active hormone to its more recently described effects on peripheral vascular tone. Basal renal renin secretion in vitro in rat kidney slices was studied in the presence of salmon calcitonin (SCT, 4400 U/mg), amino acid substituted analogues of SCT, 16-alanine SCT (6200 U/mg) and 12,16,19 tri-alanine SCT (350 U/mg), and of rat calcitonin gene-related peptide (rCGRP). All calcitonin species at the same hypocalcemic activity (1 U/mL) modestly but significantly suppressed renin secretion from control levels (9.79 +/- 0.44 to 7.51 +/- 0.53, 7.70 +/- 0.72, and 7.78 +/- 0.90 Goldblatt units/g/h for SCT, 16-ala SCT, and tri-ala SCT, P less than .05 for all calcitonins v control), whereas rCGRP had no effect. Thus, on a molar basis, the renin suppressing effects of the various calcitonin species paralleled their bioassay-defined calcium sequestering activity, 16-ala SCT greater than SCT much greater than tri-ala SCT. Lower concentrations of SCT (10(-2) U/mL and 10(-4) U/mL, approximately 6 X 10(-10) and 6 X 10(-12) mol/L, respectively) had virtually identical effects. Moreover, verapamil (5 X 10(-6) mol/L) blocked the SCT-induced suppression of renin secretion (9.79 +/- 0.44 v 9.36 +/- 1.05 GU/g/h, P = NS). We conclude that the juxtaglomerular apparatus is a calcitonin-responsive system, in which calcitonin and its analogues act to suppress basal renin secretion in vitro. This effect seems to depend on and may be mediated by modulating cellular calcium uptake, and suggests a wider, calcium-related role for calcitonin than had previously been suspected.
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PMID:Effects of calcitonin, calcitonin analogues, and calcitonin gene-related peptide on basal in vitro renin secretion. 266 71

Recent studies have shown that autoreactive B cells and autoantibodies are present in pathological as well as in normal situations. In the present study, we immortalized human B cell lines from normal individuals and from patients with malignant or benign dysglobulinemia with Epstein-Barr virus and examined, after cloning, the autoantibody reactivities of the immunoglobulins secreted by these cells. Forty-two supernatants were analyzed by enzyme-immunoassay on a panel of 13 self and non-self antigens: trinitrobenzenesulfonic acid (TNP), DNA, L-glutamine, L-alanine, L-tyrosine (GAT), actin, myosin, tubulin, albumin, renin, spectrin, transferrin, thyroglobulin, myoglobin, peroxidase, and by immunofluorescence in tissue sections. Fourteen (33%) of the immunoglobulin-secreting cell lines were found to have an autoantibody function; seven secreted IgM, six IgA, and one IgG. The light chains were of the kappa type in 11 cases. The vast majority of these clones reacted with more than five antigens of the panel and all of them reacted with TNP. No correlation was found between a given isotype and an antibody specificity. More than half of these antibodies also reacted with cellular antigens present in tissue sections. None of the four cell lines secreting monoclonal antiviral antibodies reacted with any of the antigens of the panel. The results indicate that immunoglobulins secreted by human monoclonal lymphoid cell lines can have polyspecific autoantibody functions, similar to those found in normal human polyclonal antibodies, in human monoclonal paraproteins and in natural monoclonal antibodies synthesized by murine or rat clones obtained from physiologically normal animals.
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PMID:Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus. 283 Sep 25

A 5-year-old boy is described who presented with episodes of hypoglycaemia triggered by mild infections or fever. Subnormal glucocorticoid production was confirmed by demonstrating low urinary excretion of free cortisol, low plasma cortisol concentrations that did not rise after glucagon and ACTH stimulation, and by elevated plasma ACTH levels. The selective nature of the abnormality was confirmed by demonstrating normal plasma electrolyte concentrations and blood pressure on a salt-restricted diet. Plasma renin activity and plasma aldosterone levels were also normal and responded appropriately to salt restriction and to frusemide-induced diuresis. Starvation-induced hypoglycaemia was associated with raised levels of blood ketone bodies and low blood alanine concentrations. Catecholamine secretion during hypoglycaemia was reduced. Glucocorticoid replacement therapy was effective in restoring normal glucose homeostasis.
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PMID:Isolated glucocorticoid deficiency: metabolic and endocrine studies in a 5-year-old boy. 298 94

Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.
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PMID:Highly potent and specific inhibitors of human renin. 298 28

In ten fencers at the top national level the adrenergic regulation was investigated by determining the free and sulfoconjugated catecholamines (CA) in a training fight and a competition for the national championship to evaluate the influence of emotional strain in this discipline. In the training fight which is physically more strenuous, norepinephrine (NE) was significantly higher (+27%) than in the championship contest after which the epinephrine (EPI) level was more increased (+76.5%). Accordingly, the systolic blood pressure (SBP) was higher during competition and correlated with EPI. The share of the sulfated CA in their total amount was reduced in both loads. Since energy production in fencing is predominantly alactacitic during maximal loads of short duration and aerobic during submaximal load intensities, the lactate level in the training fight was below the anaerobic/aerobic threshold. The significantly higher lactate, glucose, and alanine levels during the fight for the national championship, presumably induced by the additional stimulation of the anaerobic muscular and hepatic glycogenolysis as well as muscular glycolysis, may be accounted to the fortified EPI secretion caused by emotional strain. The higher cortisol and renin levels may be explained by the strong central stimulation and the direct peripheral effect of EPI respectively.
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PMID:Sympathoadrenergic regulation in elite fencers in training and competition. 305 75


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