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)

Water movements across the rumen wall were studied during rehydration in four fistulated sheep. The animals were dehydrated for 48 h which increased total plasma protein, plasma osmolality, plasma Na+, arginine vasopressin and plasma renin activity. Two series of experiments were performed: Expt I with no food available during rehydration, and Expt II where the animals were fed hay. On the rehydration day, a fluid marker (cobalt-EDTA) was administered into the rumen. To avoid water outflow from the rumen a stopper was inserted into the reticulo-omasal orifice. When the animals were provided with water they immediately drank 9 l. The water offered contained the same marker concentration (Co2+) as in the rumen liquid. In Expt I, Co2+ concentration increased after drinking, and remained elevated until the stopper was removed. The highest value was obtained after 20 min, and this corresponded to at least a 11 water absorption in individual animals. In Expt II, the sheep immediately started to eat following drinking and the inflow of saliva caused a dilution of the marker. Plasma osmolality and Na+ concentration decreased in both experiments indicating that water absorption occurred in both experiments. Removal of the stopper did not cause any significant changes in the parameters measured. Vasopressin concentration fell immediately on the sight of water, and then continued to decrease. It is concluded that in the sheep, voluntary drinking is followed by an immediate and substantial absorption of water from the rumen.
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PMID:Fluid absorption from the rumen during rehydration in sheep. 231 May 59

The effect of endothelin, a newly identified endothelium-derived vasoconstrictor peptide, on renin release from rat kidney cortical slices was examined. Endothelin produced a concentration-dependent inhibition of renin release and this inhibitory effect was dependent on extracellular calcium. The dihydropyridine calcium channel blockers nifedipine and nicardipine did not antagonize the inhibitory effect induced by endothelin. On the other hand, nifedipine completely antagonized the extracellular high potassium- or Bay K 8644-induced inhibition of renin release. The endothelin-induced inhibition of the release was markedly blocked by the addition of Co2+. Similar blocking effects of Co2+ were also observed with extracellular high potassium or Bay K 8644. Thus, endothelin exerts an inhibitory action on renin release in vitro, in a calcium-dependent manner. This inhibition may be mediated by the increased calcium influx through dihydropyridine-insensitive calcium channels.
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PMID:The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro. 246 32

Because adenosine plays a role in the regulation of glomerular filtration rate and of the release of renin, we examined the possibility of a local source for this mediator. We found that rat cultured glomerular mesangial cells converted 5'-AMP into adenosine. The properties of the enzyme involved in the reaction were those of an ecto-5' nucleotidase: (1) the products of the reaction were generated in the extracellular fluid although no 5'-nucleotidase was released by the cells into the medium; (2) identical activities were found for cultured cells in situ and sonicated cells; (3) the diazonium salt of sulfanilic acid which is a nonpenetrating reagent inhibited up to 75% of the enzyme activity. Ecto-5'-nucleotidase activity of intact cells obeyed Michaelis-Menten kinetics. Apparent Km for 5'-AMP was 0.32 mM. 5'-UMP was a strictly competitive inhibitor. ADP exerted a very powerful inhibitory effect and behaved also as a competitive inhibitor. ATP was inhibitory both by increasing Km and by decreasing Vmax. Ecto-5'-nucleotidase was active in the absence of divalent cations. However, Mg2+, Ca2+, Co2+ and Mn2+ were stimulatory. Zn2+ and Cu2+ suppressed the activity. Concanavalin A, a plant lectin, was markedly inhibitory, suggesting that a glycoprotein moiety was necessary to express enzyme activity. Ecto-5'-nucleotidase activity was not modified during phagocytosis of serum-treated zymosan by mesangial cells. Rat cultured glomerular epithelial cells exhibited a 5'-nucleotidase activity which was 4 times lower than that of the mesangial cells in primary culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ecto-5'-nucleotidase of cultured rat mesangial cells. 285 4

Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. We found that the decreased response of renin release from rat kidney cortical slices in high potassium solution (20-80 mM) changed to a strikingly increased one in the presence of nifedipine at doses over 10(-6) M. We then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd2+, Co2+, and Mn2+ (0.1-3.0 mM) blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in 3H efflux from the slices preloaded with [3H]norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of beta-adrenoceptors.
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PMID:Stimulatory effects of neuronally released norepinephrine on renin release in vitro. 305 10

Stimulatory effects of extracellular high K+ in the presence of nifedipine (NIF) on renin release (RR) from kidney cortical slices were investigated. The stimulation was suppressed either by propranolol or by metoprolol but not by prazosin. High K+ plus NIF-induced increase in RR was attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in Ca2+-free buffer or in medium containing divalent cations such as Cd2+, Co2+ and Mn2+. These alterations in RR correlated with 3H-efflux from the slices preloaded with 3H-norepinephrine. We conclude that the high K+ plus NIF-induced increase in RR from the slices is mediated by norepinephrine (NE) derived from renal sympathetic nerves and that this neuronally released NE stimulates RR via the activation of beta-adrenoceptors.
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PMID:Stimulatory effects of neuronally released norepinephrine on renin release from rat kidney cortical slices. 306 33

Utilizing primary cultures of mouse renal juxtaglomerular cells we found that renin secretion during 20 h of incubation was stimulated by 100% when extracellular calcium was lowered from a basal level of 0.5 mM to below 1 microM, and was enhanced in a concentration-dependent fashion by 600% when extracellular calcium was increased up to 10 mM. The stimulatory effect of low calcium on renin secretion was apparent after the first hour of incubation, whereas the stimulatory effect of increased calcium occurred with a delay of at least 1 h. During the first hour of incubation increased extracellular calcium blunted the stimulation of renin secretion induced by forskolin (10 microM). The stimulatory effect of increased calcium was attenuated in the presence of 8-pCPT-cGMP, a membrane-permeable cGMP analogue, and in the presence of 100 mM sucrose. The stimulatory effect of increased calcium was blunted in the presence of 0.5 mM cobalt, which itself stimulated renin secretion at normal (0.5 mM) calcium concentrations. Renin synthesis by the cultured cells at low calcium was markedly attenuated in proportion with total protein synthesis, whereas renin synthesis was not altered at increased calcium concentrations. Our findings suggest that a rise of intracellular calcium, induced by an increase of extracellular calcium, is associated with a transient inhibition followed by a marked and regulatable stimulation of renin secretion. Neither calcium depletion nor calcium elevation appears to exert specific effects on renin synthesis in juxtaglomerular cells.
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PMID:Extracellular calcium exerts a dual effect on renin secretion from isolated mouse juxtaglomerular cells. 838 65

A novel metallocarboxypeptidase (PfuCP) has been purified to homogeneity from the hyperthermophilic archaeon, Pyrococcus furiosus, with its intended use in C-terminal ladder sequencing of proteins and peptides at elevated temperatures. PfuCP was purified in its inactive state by the addition of ethylenediaminetetraacetic acid (EDTA) and dithiothreitol (DTT) to purification buffers, and the activity was restored by the addition of divalent cobalt (K, = 24 +/- 4 microM at 80 degrees C). The serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) had no effect on the activity. The molecular mass of monomeric PfuCP is 59 kDa as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 58 kDa by SDS-PAGE analysis. In solution, PfuCP exists as a homodimer of approximately 128 kDa as determined by gel filtration chromatography. The activity of PfuCP exhibits a temperature optimum exceeding 90 degrees C under ambient pressure, and a narrow pH optimum of 6.2-6.6. Addition of Co2+ to the apoPfuCP at room temperature does not alter its far-UV circular dichroism (CD) or its intrinsic fluorescence spectrum. Even when the CoPfuCP is heated to 80 degrees C, its far-UV CD shows a minimal change in the global conformation and the intrinsic fluorescence of aromatic residues shows only a partial quenching. Changes in the intrinsic fluorescence appear essentially reversible with temperature. Finally, the far-UV CD and intrinsic fluorescence data suggest that the overall structure of the holoenzyme is extremely thermostable. However, the activities of both the apo and holo enzyme exhibit a similar second-order decay over time, with 50% activity remaining after approximately 40 min at 80 degrees C. The N-blocked synthetic dipeptide, N-carbobenzoxy-Ala-Arg (ZAR), was used in the purification assay. The kinetic parameters at 80 degrees C with 0.4 mM CoCl2 were: Km, 0.9 +/- 0.1 mM; Vmax, 2,300 +/- 70 U mg(-1); and turn over number, 600 +/- 20 s(-1). Activity against other ZAX substrates (X = V, L, I, M, W, Y, F, N, A, S, H, K) revealed a broad specificity for neutral, aromatic, polar, and basic C-terminal residues. This broad specificity was confirmed by the C-terminal ladder sequencing of several synthetic and natural peptides, including porcine N-acetyl-renin substrate, for which we have observed (by MALDI-TOF MS) stepwise hydrolysis by PfuCP of up to seven residues from the C-terminus: Ac-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser.
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PMID:Purification and characterization of a cobalt-activated carboxypeptidase from the hyperthermophilic archaeon Pyrococcus furiosus. 1059 52

Nicotianamine (NA) is a nonprotein amino acid that inhibits the angiotensin I-converting enzyme (ACE) in the renin-angiotensin system (RAS). The purpose of this study is to prove that NA contributes to the suppression of hypertension by preferential inhibition of ACE. On comparison with EDTA-a chelator-we found that the inhibition pattern of NA for ACE is that of mixed inhibition and that NA exhibits weak chelation effects for zinc, copper, and cobalt ions. Therefore, we investigated whether NA inhibited zinc-containing enzymes other than ACE in vitro. The results revealed that NA does not inhibit leucine aminopeptidase or alkaline phosphatase in rat serum. On the other hand, NA demonstrated specific inhibitory effects for rat serum ACE and aortic ACE. These results suggest that the preferential inhibition of circulatory and tissue ACE by NA can contribute to the suppression of hypertension.
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PMID:Nicotianamine preferentially inhibits Angiotensin I-converting enzyme. 1793 38

Gap junctional intercellular communication (GJIC) plays a critical role in the control of multiple cell behavior as well as in the maintenance of tissue and organ homeostasis. However, mechanisms involved in the regulation of gap junctions (GJs) have not been fully understood. Given endoplasmic reticulum (ER) stress and dysfunction of GJs coexist in several pathological situations, we asked whether GJs could be regulated by ER stress. Incubation of mesangial cells with ER stress-inducing agents (thapsigargin, tunicamycin, and AB(5) subtilase cytotoxin) resulted in a decrease in connexin 43 (Cx43) expression at both protein and mRNA levels. This was accompanied by a loss of GJIC, as evidenced by the reduced numbers of dye-coupled cells after single cell microinjection or scrape loading dye transfer. Further studies demonstrated that ER stress significantly inhibited the promoter activity of the Cx43 gene, reduced [(35)S]-methionine incorporation into Cx43 protein and accelerated degradation of Cx43. ER stress also decreased the Cx43 protein levels in several different cell types, including human umbilical vein endothelial cells, mouse-derived renin-secreting cells and human hepatoma cells. Furthermore, induction of ER stress by hypoxic chemicals thenoyltrifluoroacetone and cobalt chloride was found to be associated with a reduction in Cx43. Our findings thus reveal a close link between ER stress and GJs. ER stress may represent a novel mechanism underlying the altered GJs in a variety of pathological situations.
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PMID:Downregulation of gap junction expression and function by endoplasmic reticulum stress. 1949 36

Inhibition of prolyl hydroxylase domain-containing protein (PHD) by hypoxia stabilizes hypoxia-inducible factor 1 and increases the expression of target genes, such as vascular endothelial growth factor. Although the systemic renin-angiotensin system is activated by hypoxia, the role of PHD in the regulation of the renin-angiotensin system remains unknown. We examined the effect of PHD inhibition on the expression of angiotensin II type 1 receptor (AT(1)R). Hypoxia, cobalt chloride, and dimethyloxalylglycine, all known to inhibit PHD, reduced AT(1)R expression in vascular smooth muscle cells. Knockdown of PHD2, a major isoform of PHDs, by RNA interference also reduced AT(1)R expression. Cobalt chloride diminished angiotensin II-induced extracellular signal-regulated kinase phosphorylation. Cobalt chloride decreased AT(1)R mRNA through transcriptional and posttranscriptional mechanisms. Oral administration of cobalt chloride (14 mg/kg per day) to C57BL/6J mice receiving angiotensin II infusion (490 ng/kg per minute) for 4 weeks significantly attenuated perivascular fibrosis of the coronary arteries without affecting blood pressure level. These data suggest that PHD inhibition may be beneficial for the treatment of cardiovascular diseases by inhibiting renin-angiotensin system via AT(1)R downregulation.
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PMID:Inhibition of prolyl hydroxylase domain-containing protein downregulates vascular angiotensin II type 1 receptor. 2182 25


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