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

The anatomical relationship between kallikrein and renin in the rat kidney was investigated immunohistochemically by the peroxidase-antiperoxidase method. Kallikrein was localized to the convoluted distal tubule, starting at a point, distal to the juxtaglomerular apparatus, where the thick ascending limb of loop of Henle transformed into the convoluted distal tubule. The thick ascending limb was identified by its content of uromucoid (Tamm-Horsfall glycoprotein). Kallikrein was never observed within the juxtaglomerular apparatus itself. The kallikrein-containing tubule ended where the distal tubule submerged into the collecting duct. Renin was found in epitheloid cells of the afferent arteriole. When neighboring sections were stained for kallikrein and renin, respectively, no close anatomical relationship was observed between the kallikrein-containing and the renin-containing structures.
 ...
PMID:Localization of kallikrein in the rat kidney and its anatomical relationship to renin. 703 45

Captopril, a competitive inhibitor of angiotensin I-converting enzyme (ACE), is an orally potent antihypertensive agent. Light and electron microscopic studies of th kidneys of mice, rats, and monkeys given large oral doses of captopril for long duration were conducted. All mice and some rats and monkeys developed hyperplasia of the renin-secreting cells which appeared in several layers surrounding the vascular wall of the afferent arterioles. In the electron microscope, these epithelioid cells appeared heavily loaded with aggregates of homogeneous electron dense, osmiophilic amorphous granules filling distended spaces of the endoplasmic reticulum. The Golgi cisterns often included small, sharply outlined triangular or rhomboid osmiophilic granules. The use of specific renin antibodies and the application of the "three-layer bridge technique" for peroxidase-antiperoxidase defined and verified the accumulation of renin in the juxtaglomerular cells. After cessation of dosing, hyperplasia of the juxtaglomerular cells markedly regressed, and there was a significant reduction in the number and size of the renin granules in such cells.
 ...
PMID:Hyperplasia of juxtaglomerular cells and renin localization in kidney of normotensive animals given captopril. Electron microscopic and immunohistochemical studies. 704 18

The effect of the lysosomal contents of hog kidney cortex, especially of the fraction not bound by concanavalin A (Fraction A) on the permeability of the coronary and cerebral arteries of rats was studied ultrastructurally using H.R. peroxidase. This fraction was devoid of renin activity by bioassay. The coronary arteries of the experimental rats displayed fibrinoid degeneration: e.g., degeneration and disappearance of medial smooth muscle cells and deposition of electron dense materials containing fibrin. A large amount of reaction product of peroxidase was present in the subendothelial space and media where fibrinoid degeneration was evident. Transendothelial passage of the marker occurred by both junctional and vesicular transport. There was no evidence of separation or discontinuity of the endothelial cells. Occasionally, increased permeability of the intima was noted in the coronary arteries without medial damage. By contrast, neither fibrinoid degeneration nor increased permeability was noted in the cerebral arteries. The difference in the response of the two arteries seems attributable to the barrier effect of cerebral arterial intima.
 ...
PMID:Fibrinoid degeneration and increased vascular permeability induced by renal lysosomal contents. An electron microscopic study on coronary and cerebral arteries of rats. 736 64

The distribution and content of renin in Sprague-Dawley (SD) and transgenic (mREN-2)27 rats (TG) were compared to further define the cellular basis and function of the adrenal renin-angiotensin system. Antibody binding (to rat and mouse renin protein and prosequence) was visualised in serial paraffin sections using an avidin-biotin peroxidase technique. Chromaffin and adrenaline cells were identified by tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase immunoreactivity, respectively. In SD zona glomerulosa (ZG), renin and its prosequence localised to small steroid cells while in homozygous (receiving lisinopril) and heterozygous (untreated) TG, steroid cells labelled in all cortical zones. In addition, throughout the cortex of each strain, large polyhedral adrenaline chromaffin cells occurring singly or in small groups and occasionally in rays labelled for renin and prosequence. Similar large adrenaline cells immunolabelled for all antisera in medulla while other cells were only TH-positive. Total adrenal renin content was 53 times higher in heterozygous transgenics than SD rats and was mainly (74%) prorenin. In SD, 37% of cortical renin was prorenin but in adrenal medulla only active renin was detected. Thus, from present and previous work both renin and prorenin occur not only in mitochondrial dense bodies of the ZG, but also in secretory granules of adrenaline chromaffin cells in both cortex and medulla implying in situ synthesis and paracrine functions.
 ...
PMID:Adrenaline cells of the rat adrenal cortex and medulla contain renin and prorenin. 880 37

To obtain evidence of renin-synthesizing cells in the murine coagulating gland (CG), CG renin mRNA was detected by hybridohistochemistry, as well as in vitro reverse transcriptase-polymerase chain reaction (RT-PCR) in intact, castrated and testosterone-treated C57BL/6 mice. Hybridohistochemistry using paraffin sections of the kidneys and the CGs for the detection of renin mRNA was performed with digoxigenin-labelled probes. Some paraffin sections were immunohistochemically stained for renin by the peroxidase-anti-peroxidase method. Total RNA was extracted, incubated by reverse transcriptase, and amplified by PCR. In the kidneys, the immunoreactivity and the positive signals of hybridohistochemistry using an antisense probe were restricted to the same juxtaglomerular cells. In the control and at 7 days after testosterone administration to castrated mice, both renin-immunoreactivity and -hybridoreactivity were expressed by the epithelial cells in the CGs, while, in the CGs of the castrated mice and 3 days after testosterone injection of castrated animals, neither renin-immunoreactivity nor -hybridoreactivity was detected in the epithelial cells. Using RT-PCR, renin mRNA from the mice in the control and 7 days after testosterone injection of castrated was amplified, whereas, in the castrated and the 3 days after testosterone injection of castrated groups, it was not detected. The data presented here provide additional evidence that CG renin is regulated by testosterone.
 ...
PMID:Detection of coagulating gland renin by hybridohistochemistry. 901 Nov 6

Captopril (D-3-mercapto-2-methylpropanoyl-L-proline) is an angiotensin converting enzyme (ACE) inhibitor, used widely in the treatment of hypertension and congestive heart failure. Captopril also inhibits proliferation of a variety of cell types, including several lacking ACE and renin acitvity. We have previously demonstrated that human mammary ductal carcinoma cells are among the cell types whose mitotic activity is inhibited by captopril. In those cells, captopril also reduces estrogen receptor (ER) and increases progesterone receptor (PR) concentrations. The present study evaluated the mechanism of captopril's antiproliferative action in an ER/PR-negative human mammary ductal carcinoma cell line, Hs578T. Cells grown in a 10% serum medium showed negligible changes in the presence of captopril alone. However, in the presence of subphysiologic concentrations of copper salts or copper-loaded ceruloplasmin, captopril caused a dose-dependent reduction in cell number, thymidine incorporation and mitochondrial dehydrogenase activity. In contrast, iron salts and iron-saturated transferrin had no effect on captopril activity. Catalase and horseradish peroxidase nullified the cytotoxic effects of captopril/Cu++, whereas H2O2 mimicked those effects. These data are consistent with the notion of a copper-catalyzed oxidation of captopril, leading to the generation of H2O2 as the cytotoxin to this clinically important cell type.
 ...
PMID:Mechanism of captopril toxicity to a human mammary ductal carcinoma cell line in the presence of copper. 1051 67

Renin-binding protein (RnBP) is a highly specific renin inhibitor first isolated from porcine kidney. Our recent studies demonstrated that the human RnBP is the enzyme N-acetyl-D-glucosamine (GlcNAc) 2-epimerase [Takahashi, S. et al. (1999) J. Biochem. 125, 348-353]. We have developed a new assay method for GlcNAc 2-epimerase activity using a system of N-acyl-D-hexosamine oxidase coupled with peroxidase and employed this method to study the effects of renin on GlcNAc 2-epimerase activity. The recombinant human (rh) RnBP existed as a dimer and its GlcNAc 2-epimerase activity was strongly inhibited by the purified renin concomitant with the formation of RnBP-renin heterodimer, so-called high molecular weight (HMW) renin. The renin activity was also inhibited by rhRnBP in a dose-dependent manner. These results indicate that renin is an inhibitor of GlcNAc 2-epimerase, and the renin-RnBP heterodimer HMW renin is an inactive form of both renin and GlcNAc 2-epimerase activities.
 ...
PMID:Renin inhibits N-acetyl-D-glucosamine 2-epimerase (renin-binding protein). 1109 37

The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10 mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-beta (TGF-beta 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-beta's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p < 0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system.
 ...
PMID:Histopathological and ultrastructural effects of Losartan on embryonic rat kidney. 1618 65

Metabolic aromatization of xenobiotics is an unusual reaction with some documented examples. For instance, the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the neurotoxic pyridinium ion metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase (MAO) B in the brain has been of interest to a number of investigators. It has also been reported that although the aromatization of N-methyl-tetrahydroisoquinoline occurs with MAO B, the metabolism does not proceed for its isomer, N-methyl-tetrahydroquinoline, by the same enzyme. The aromatization of an N-alkyl-tetrahydroquinoline substructure was identified during in vitro metabolite profiling of compound A, which was designed as a potent renin inhibitor for the treatment of hypertension. The N-alkylquinolinium metabolite of compound A was identified by liquid chromatography-tandem mass spectrometry of human liver microsomal incubates and proton NMR of the isolated metabolite. Further in vitro metabolism studies with a commercially available chemical (compound B), containing the same substructure, also generated an N-alkylquinolinium metabolite. In vitro cytochrome P450 (P450) reaction phenotyping of compound A revealed that the metabolism was catalyzed exclusively by CYP3A4. Although compound B was a substrate for several P450 isoforms, its quinolinium metabolite was also generated predominantly by CYP3A4. Neither compound A nor compound B was a substrate of MAOs. The quinolinium metabolites were readily produced by horseradish peroxidase, suggesting that aromatization of the N-alkyltetrahydroquinoline could occur via a mechanism involving single electron transfer from nitrogen. Although dihydro intermediates from the tetrahydroquinoline substrates were not observed in the formation of quinolinium metabolites, cyanide trapping results indicated the occurrence of iminium intermediates.
 ...
PMID:Metabolic aromatization of N-alkyl-1,2,3,4-tetrahydroquinoline substructures to quinolinium by human liver microsomes and horseradish peroxidase. 1698 99

Angiotensin receptor blockers enhance endothelial function and are suggested to improve erectile function. The effects and underlying mechanisms of treatment with the angiotensin receptor blocker irbesartan on penile endothelial function in apolipoprotein E (ApoE)(-/-) mice were determined. Wild-type (C57/B6) and ApoE(-/-) mice were fed with a high-fat, cholesterol-rich diet for 7 weeks and treated with irbesartan (50 mg/kg . day) or hydralazine (250 mg/l). Vital parameters were measured with the tail-cuff method. Endothelial (aortic rings) and erectile function (corpora cavernosa) were assessed by pharmacological stimulation in an organ bath chamber. Oxidative stress and angiotensin receptor expression were determined. Blood pressure was significantly decreased in irbesartan- and hydralazine-treated ApoE(-/-) mice (p < 0.05) compared with controls and wild-type mice. Endothelial function of the aorta and corpus cavernosum was significantly impaired in ApoE(-/-) mice (p < 0.05) and could be restored by treatment with irbesartan (p < 0.05). Consistently, nitric oxide production of corpora cavernosa was impaired in ApoE(-/-) mice (p < 0.01), with a restoration in irbesartan- but not hydralazine-treated mice. Dihydroethidium-stained sections and lipid peroxidase assay revealed a reduction of superoxide production in irbesartan (p < 0.05) compared with hydralazine-treated and control ApoE(-/-) mice. In summary, irbesartan improves penile endothelial function in ApoE(-/-) mice by reduction of vascular and cavernosal oxidative stress. This result emphasizes the beneficial effect of inhibition of the renin-angiotensin system even in terms of erectile function.
 ...
PMID:Improvement of endothelial function of the corpus cavernosum in apolipoprotein E knockout mice treated with irbesartan. 1881 94


<< Previous 1 2 3 4 5 Next >>