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)

A simple fluorimetric assay was set up to test renin within 2 h. N-acetyltetradecapeptide was synthesized and used as substrate. It was demonstrated that N-acetyl-angiotensin I and Leu-Val-Tyr-Ser were the two peptides obtained after hydrolysis by renin. Fluorescamine reaction reacted with the free NH2 of the tetrapeptide generated to induce a fluorimetric reaction detected at 395--405 nm. The Michaelis constant of the reaction was 1.87 . 10(-5) M. With this method as little as one milliGoldblatt Unit (mG.U.) of hog renin could be detected and the generation of tetrapeptide was linear with respect to the renin concentration up to 20 mG.U. The fluorimetric assay was applied to the detection of renin during its purification and to the characterization of renin inhibitors.
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PMID:Fluorimetric assay of renin. 56 20

Hypoxia and the hypercapnia were produced in anesthetized dogs by artificial respiration with appropriate gas mixtures, and a study was conducted of the effects of these conditions on various metabolic parameters, viz. catecholamines, renin activity, lactate, pyruvate, cortisol, non-esterified free fatty acids (FFA), and ammonia, in the plasma of the arterial blood. Hypercapnia caused a distinct increase in catecholamine concentrations, renin activity and ammonia, and a decrease in lactate and pyruvate; cortisol and FFA levels were only slightly altered. Hypoxia increased lactate, pyruvate and--though only to a slight extent--FFA, cortisol and NH3. The changes induced by hypercapnia were chiefly attributable to activation of the sympathico-adrenal system; those induced by hypoxia were not.
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PMID:[Metabolic effects of acute experimental hypoxia and hypercapnia]. 92 42

The following active site directed inactivators for the pressor enzyme renin were synthesized: L-alpha-bromo-isocaproyl(BIC)-Leu-Val-Tyr-Ser-OH, L-BIC-Val-Tyr-Ser-OH, L-BIC-Leu-Val-OCH3, L-BIC-Leu-Val-OH, L-BIC-Val-Tyr-NH2, L-BIC-Val-Tyr-OCH3, L-BIC-Val-Tyr-OH, L-BIC-Leu-OCH3, L-BIC-Val-OCH3, and L-BIC-OCH3. The rate of inactivation of mouse submaxillary gland renin by these reagents was studied under a variety of conditions. L-alpha-Bromoisocaproyl-Val-Tyr-Ser-OH and L-alpha-bromoisocaproyl-Leu-Val-Tyr-Ser-OH and L-alpha-bromoisocaproyl-Leu-Val-Tyr-Ser-OH were the most efficient inactivators followed by L-alpha-bromoisocaproyl-Val-Tyr-NH2. The rates of inactivation by the first two peptides were strongly dependent on pH, being most efficient at low pH, least efficient at pH near 5.6, and becoming efficient again at neutral pH. The rate of the inactivation by L-alpha-bromoisocaproyl-Val-Tyr-NH2, in which the C-terminal carboxyl group is blocked, was only slightly dependent on pH. Complete inactivation was achieved by these three reagents. The inactivation was accompanied by incorporation of a stoichiometric quantity of the radiolabeled reagents. Based on these findings it was concluded that the inactivators reacted with a carboxyl group(s) in the active site of the renin molecule to form an esteric linkage. These data also suggest that a carcoxyl group(s) may constitute part of the catalytically essential functional groups in renin action. D-alpha-Bromoisocaproyl derivatives of the various peptides mentioned above were also prepared. These compounds were much less active than the L isomers indicating that the inactivation by the L-alpha-bromoisocaproyl peptides was a specific reaction.
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PMID:Active site directed inactivators of mouse submaxillary renin. 114 98

We have investigated whether binding parameters and subtypes of glomerular, papillary, and vascular atrial natriuretic factor (ANF) receptors differ in rats with moderate high-output heart failure [aortocaval (AC) shunt] from their sham-operated controls. Body weight was lower and relative heart weight was higher in the AC shunt group than in the control group. Plasma renin activity (PRA) was also greater in AC shunt rats. Plasma COOH- and NH2-terminal ANF levels were higher in AC shunt animals than in their control counterparts. Total atrial ANF content was elevated in both the right and left atria of the AC shunt group. Glomerular and papillary ANF receptor density (Bmax) and ANF receptor affinity (Kd) were similar in both AC shunt and control rats. Vascular ANF receptor density and affinity were lower in AC shunt (Bmax = 65 +/- 13 fmol.mg protein; Kd = 467 +/- 52 pM) than in control rats (Bmax = 188 +/- 34 fmol.mg protein; Kd = 278 +/- 11 pM). Irreversible cross-linking of 125I-labeled ANF followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and radioautography demonstrated that both high- and low-molecular weight receptors were unchanged in glomerular membranes and downregulated in vascular membranes from AC shunt animals. However, guanosine 3',5'-cyclic monophosphate (cGMP) production by the isolated glomeruli of AC shunt rats was lower than that of controls. We conclude that in the presence of elevated plasma ANF levels, glomerular, papillary, and vascular ANF receptors may be regulated differently.
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PMID:Divergent regulation of atrial natriuretic factor receptors in high-output heart failure. 133 15

Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.
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PMID:Design of potent substrate-analogue inhibitors of canine renin. 144 72

The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldosterone, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinaemia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120-180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver renal haemodynamic response to a meat meal is independent of changes in glucagon.
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PMID:Glucagon-independent renal hyperaemia and hyperfiltration after an oral protein load in Child A liver cirrhosis. 155 40

The present study investigated the sensitivity of the medial region of the amygdala to the antinatriorexic action in the rat of the tachykinins eledoisin, substance P, neurokinin A and [Asp5,6, MePhe8] substance P(5-11) (also referred to as amino-senktide; NH2-SENK), which is a highly selective agonist for NK-3 receptors. The results obtained show that only the potent NK-3 agonists eledoisin and NH2-SENK inhibit salt appetite when injected into the medial region of the amygdala. Eledoisin and NH2-SENK inhibited salt appetite induced by sodium depletion, that has been proven to be governed by the synergism of angiotensin and aldosterone. They inhibited also salt appetite evoked by central renin injection, that is due to production of angiotensin II. On the other hand, eledoisin and NH2-SENK did not inhibit salt appetite evoked by subcutaneous deoxycorticosterone treatment. These findings suggest that the medial region of the amygdala is a site of action for the antinatriorexic effect of tachykinins and that their action at this site is mediated by NK-3 receptors. Moreover, our results show that in the medial amygdala, the antinatriorexic action of tachykinins appears to be directed toward the angiotensinergic component of the neural mechanism for salt appetite.
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PMID:Inhibition of salt appetite in the rat following injection of tachykinins into the medial amygdala. 169 38

The cardiovascular effects of a novel enkephalin analogue, 443C81 (Tyr-D-Arg-Gly-Phe(4NO2)-Pro.NH2), were studied in healthy volunteers. According to a double-blind, cross-over, randomised, balanced design, six men received two different doses of 443C81 or saline as intravenous (i.v.) infusions on three occasions. Mean +/- SD plasma concentrations achieved at steady state were 0.46 +/- 0.11 microgram/ml after low-dose 443C81 and 1.0 +/- 0.2 microgram/ml after high-dose 443C81. In the supine position, low and high doses produced mean transient increases in diastolic blood pressure (DBP) of 5 and 4 mm Hg and heart rate (HR) of 5 and 12 beats/min, respectively. With the higher dose, these changes were followed by a mean decrease in DBP of 8 mm Hg while HR returned to control values. When the subjects were tilted, the pressor effect was not observed, and hypotension occurred earlier and was more pronounced. Both doses reduced forearm and systemic vascular resistance, and there was a dose-related increase in supine forearm venous capacitance; venoconstriction associated with tilting was unaffected by 443C81. Plasma renin activity and elevation of epinephrine concentrations on tilting were increased by the enkephalin, which also caused a diuresis through an increase in free water clearance.
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PMID:Cardiovascular effects of a novel enkephalin analogue, 443C81, in humans. 170 Feb 18

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH2 ), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH2 with a Km value of 3.4 x 10(-5) M, at pH 7.3 and 37 degrees being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the Vmax value of 4.1 x 10(-9) mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu10-Val11 bond and, surprisingly, His9-Leu10 as well.
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PMID:Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin. 179 5

Synthetic peptides described as dog renin inhibitors were found to effectively inhibit the aspartyl protease of human immunodeficiency virus (HIV). The selection of oligopeptides for the HIV protease inhibition study was based on 1) the current strategy of inhibiting aspartyl proteases with transition state analogs, and 2) our previous observations regarding optimal structural differentiation at the P2 position among human, dog, and rat renin inhibitors. In an in vitro assay system consisting of recombinant HIV protease and a synthetic decapeptide substrate (at pH 5.5), results show that HIV protease was unaffected by statine-containing analogs carrying histidine at the P2 position whereas analogs containing valine at the same position yielded anti-protease IC50 values ranging from 50 to 500 nM. As anticipated, some analogs were also shown to inhibit processing of recombinant polyprotein substrate by HIV protease in vitro. The anti-viral activity of three inhibitors was studied in HIV-infected CEM and MT-2 cells. Results showed that one compound, Ac-Naphthylalanyl-Pro-Phe-Val-Statine-Leu-Phe-NH2 (antiprotease IC50 value = 0.4 microM), protected the infected cells effectively with IC50 values (0.73 microM for CEM cells and 0.88 microM for MT-2 cells). This antiviral effect is comparable to those obtained with AZT and ddC in parallel studies of MT-2 cells.
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PMID:A rational approach in the search for potent inhibitors against HIV proteinase. 186 85


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