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)

Tissue kallikrein gene expression in rat kidney was examined by in situ hybridization histochemistry. A rat tissue kallikrein cDNA probe, 534 bases in length and complementary to the 3' end of kallikrein mRNA was first used in Northern blot analysis to demonstrate the existence of tissue kallikrein mRNA in rat kidney. Then, kallikrein mRNA's localization in rat kidney sections was studied in situ hybridization histochemistry using the same probe. Positive signals were concentrated in the renal cortex at the vascular pole of the glomeruli and to a lesser degree, the distal tubular cells. Prehybridization with the unlabeled probe can abolish the positive signal; the same result can also be achieved by pretreatment of the tissue section with ribonuclease. By using the same technique, tissue kallikrein mRNA was also localized in granular convoluted tubule and striated duct cells of rat submandibular gland. The results suggest a new site of renal kallikrein synthesis at the vascular pole of the glomerulus. These findings, coupled with the previous studies that tissue kallikrein can participate in activation and releasing of renin, raise a potential physiological role of kallikrein in renin release or prorenin processing at juxtaglomerular cells.
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PMID:Renal kallikrein mRNA localization by in situ hybridization. 277 Jan 12

The level of tissue kallikrein in serum and urine, and of an erythrocyte kallikrein-like enzyme, were compared in 10 subjects without hypertension and in 10 patients with hypertension with normal renin levels. Each group consisted of five men and five women. All subjects were observed at a general clinical research center for consecutive 5- to 6-day periods of daily dietary sodium intake of 109, 9, and 259 mEq. Tissue kallikrein levels in serum and urine and levels of the erythrocyte kallikrein-like enzyme were measured with specific radioimmunoassays or with an activity assay, respectively. Mean active and total urinary kallikrein excretion rates were higher in women than in men (both with and without hypertension) when they were given all diets (p less than 0.05 to 0.025), and these rates varied inversely with sodium intake. The serum immunoreactive tissue kallikrein level was higher in men than in women when they were given all diets (p less than 0.05 to 0.001), but there was no difference between subjects with and without hypertension. There were no consistent changes in levels with altered sodium intake. Erythrocyte kallikrein-like esterase activity was greater in women without hypertension than in men without hypertension (p less than 0.05 to 0.001) when receiving the 9 and 109 mEq sodium diets, but values were similar in all groups receiving the 259 mEq sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gender differences of human tissue kallikrein and an erythrocyte kallikrein-like enzyme in essential hypertension. 318 93

Four members of the tissue kallikrein family, mK1, mK9, mK13, and mK22, all of which exhibit extensive homology in amino acid sequence among themselves, were obtained from the submandibular gland of ICR mice and examined for their ability to cleave prorenin. Tissue kallikrein mK13 was confirmed to be a prorenin-converting enzyme; and mK9, which was earlier shown to be an EGF-binding protein, was found to cleave mouse Ren 2 prorenin specifically and convert it to mature renin with an activity of approximately 1/10 of that of mK13. With the same substrate, mK22 (beta-NGF endopeptidase) gave two products, renin and arginyl-renin; whereas mK1 (true tissue kallikrein) did not process it at all. The endoproteolytic activity of tissue kallikreins was examined with various peptide-MCA substrates. The substrates contained three key structures; X(Y)-Arg-Arg, X(Y)-Lys-Arg and X-Lys-Lys motifs (where X and Y are hydrophilic and hydrophobic amino acids, respectively). We found that mK1, mK9 and mK13 preferentially cleaved the former two types of substrate, except Y-Arg-Arg-MCA. The substrate X-Lys-Lys-MCA was hardly cleaved by these three tissue kallikreins but was preferentially cleaved by mK22. The four tissue kallikreins seem to have the ability to process precursor proteins containing a pair of basic amino acid residues; the specificities of three of the enzymes (mK1, mK9 and mK13) were similar to each other but were different from that of mK22.
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PMID:Prorenin processing and restricted endoproteolysis by mouse tissue kallikrein family enzymes (mK1, mK9, mK13, and mK22). 950 64

This study was addressed to evaluate the temporospatial pattern of key components of the kallikreinkinin system in human uterus in luteal phase (n = 7), early pregnancy (isolated spontaneous abortions, n = 11; ectopic pregnancies, n = 9), idiopathic preterm deliveries (n = 5), and term gestations (n = 12). Tissue kallikrein mRNA and protein and the type 2 bradykinin receptor (B2R) protein were expressed in luminal and glandular epithelium and in endothelial cells of stromal and myometrial blood vessels, while tissue kallikrein mRNA and B2R, but not tissue kallikrein protein, were observed in decidual cells and in arteriolar and myometrial muscle. A greater signal intensity for tissue kallikrein mRNA and protein and of B2R protein was observed in the early pregnancy samples. The sites and variations of the tissue kallikrein mRNA and protein and of the B2R protein in the human uterus and in fallopian tubes during the luteal phase and in pregnancy coincide with those described for other vasoactive effectors such as nitric oxide, prostacyclins, growth factors, and renin. The uterine localization of the main enzyme and receptor of the tissue kallikrein-kinin system in key sites for embryo attachment, implantation, placentation, maintenance of placental blood flow, and parturition supports the notion that the kallikreinkinin system participates in these processes, probably through vasodilation, increased vasopermeability, enhanced matrix degradation, stimulation of cell proliferation, and myometrial contractility.
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PMID:Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and in early and late gestation. 1195 65

1. Acute myocardial ischaemia and reperfusion trigger cardioprotective mechanisms that tend to limit myocardial injury. These cardioprotective mechanisms remain for a large part unknown, but can be potentiated by performing ischaemic preconditioning or by administering drugs such as angiotensin-I-converting enzyme (kininase II) inhibitors (ACEI). 2. This brief review summarizes the findings concerning the role of tissue kallikrein (TK), a major kinin-forming enzyme, kinins and kinin receptors in the cardioprotection afforded by ischaemic preconditioning (IPC) or by pharmacological postconditioning by drugs originally targeted at the renin-angiotensin system, ACEI and type 1 angiotensin-II receptor blockers (ARB) in acute myocardial ischaemia. Myocardial ischaemia was induced by left coronary occlusion and was followed after 30 min by a 3 h reperfusion period (IR), performed in vivo in mice. The role of the kallikrein-kinin system (KKS) was studied by using genetically engineered mice deficient in TK gene and their wild-type littermates, or by blocking B1 or B2 bradykinin receptors in wild-type mice using selective pharmacological antagonists. 3. Ischaemic preconditioning (three cycles: 3 min occlusion/5 min reperfusion) enhances the ability of the heart of wild-type mice to tolerate IR. Tissue kallikrein plays a major role in the cardioprotective effect afforded by IPC, which is largely reduced in TK-deficient mice. The B2 receptor is the main kinin receptor involved in the cardioprotective effect of IPC. 4. Tissue kallikrein is also required for the cardioprotective effects of pharmacological postconditioning with ACEI (ramiprilat) or ARB (losartan), which are abolished for both classes of drugs in TK-deficient mice. The B2 receptor mediates the cardioprotective effects of these drugs. Activation of angiotensin-II type 2 (AT2) receptor is involved in the cardioprotective effects of losartan, suggesting a functional coupling between AT2 receptor and TK during angiotensin-II type 1 (AT1) receptor blockade. 5. The demonstration of a cardioprotective effect of the KKS in acute myocardial ischaemia involving TK and the B2 receptor and playing a major role in IPC or pharmacological postconditioning by ACEI or ARB, suggests a potential therapeutic approach based on pharmacological activation of the B2 receptor.
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PMID:Cardioprotection and kallikrein-kinin system in acute myocardial ischaemia in mice. 1830 47

Tissue kallikrein (TK) is synthesized in arteries and distal renal tubule, the main target of aldosterone. Urinary kallikrein excretion increases in hyperaldosteronism. We tested the hypothesis that TK is involved in the cardiovascular and renal effects of high aldosterone. Kallikrein-deficient mice (TK-/-), and wild-type (WT) littermates, studied on two different genetic backgrounds, were treated with aldosterone and high-NaCl diet for 1 month. Control mice received vehicle and standard NaCl diet. Treatment induced 5- to 7-fold increase in plasma aldosterone, suppressed renin secretion, and increased urinary TK activity. In 129SvJ-C57BL/6J mice, blood pressure monitored by radiotelemetry was not different between control TK-/- and WT mice. In TK-/- mice, aldosterone induced larger increases in blood pressure than in WT mice (+47 vs. +27 mm Hg; genotype-treatment interaction, P < 0.05). Night-day difference was also exacerbated in treated TK-/- mice (P < 0.01). Moderate cardiac septal hypertrophy was observed in hypertensive animals without major change in heart function. Aldosterone-salt increased kidney weight similarly in both genotypes but induced a 2-fold increase in renal mRNA abundance of epithelial sodium channel subunits only in TK-/- mice. The hypertensive effect of TK deficiency was also documented in treated C57BL/6J mice. In this strain, aldosterone-induced hypertension was only observed in TK-/- mice (+16 mm Hg, P < 0.01). These findings show that TK deficiency exacerbates aldosterone-salt-induced hypertension. This effect may be due at least in part to enhanced sodium reabsorption in the distal nephron aggravating sodium retention. The study suggests that kallikrein plays an antihypertensive role in hyperaldosteronism.
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PMID:Antihypertensive role of tissue kallikrein in hyperaldosteronism in the mouse. 2266 97