Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We attempted to determine the level of sweat kallikrein (kininogenase) and to purify and characterize it using sweat collected over a white petrolatum barrier. Thermally induced eccrine sweat obtained from 24 healthy subjects showed kallikrein activity of 24.4 ng kinins generated/1 mg of sweat protein when heated plasma was used as the substrate and 16.1 ng kinin when purified low molecular weight bovine kininogen was used as the substrate. Sweat was sequentially purified by Sephacryl S-200, diethyaminoethyl Sephacel, and fast flow liquid chromatography Mono Q chromatography. Sweat kallikrein had a M(r) of 40,000 and was inhibited by aprotinin but not by soybean trypsin inhibitor. The peptide generated by sweat kallikrein was identified as lys-bradykinin using reverse phase high-performance liquid chromatography and by its amino acid sequence. Anti-human urinary kallikrein immunoglobulin G neutralized the sweat kallikrein activity completely, indicating that the sweat kallikrein is the glandular type. Purified sweat and salivary kallikrein showed similar M(r) and responses to inhibitors and antibodies. Using immunohistochemistry, kallikrein activity was localized in luminal ductal cells and in the peripheral rim of secretory coil segments, presumably the outer membrane of the myoepithelium. We also observed kininase activity in sweat at M(r) 160,000, which was inhibited by ethylenediamine tetraacetic acid, captopril, and angiotensin converting enzyme inhibitor peptide, indicating that it is kininase II (or angiotensin converting enzyme). Sweat also contains abundant non-kallikrein hydrolases for S-2266 and S-2302. The demonstration of glandular kallikrein, its tissue localization, and the presence of kininase II in sweat provide the basis for future studies on the physiologic role of the kallikrein/kinin system in the eccrine sweat gland.
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PMID:Human eccrine sweat contains tissue kallikrein and kininase II. 750 64

Kinins are endothelium-dependent vasodilators and natriuretic paracrine peptides that participate in the regulation of blood pressure, renal hemodynamics and sodium excretion. Several lines of evidence suggest an important role for intrarenal kinins and their receptors in kidney growth and development. (1) The developing rat kidney expresses all the components of the tissue kallikrein-kinin system: tissue kallikrein, low molecular weight (LMW) kininogen, kininase II and kinin receptors. Also, the developing liver expresses high molecular weight and LMW kininogens. Thus, a complete kinin-generating system exists in the developing kidney. (2) Gene transcription, mRNA and protein abundance, and enzymatic activity of renal kallikrein are all markedly up-regulated during postnatal kidney growth, and a positive correlation exists between renal kallikrein synthesis and the maturational rise in renal blood flow. (3) Rat glomerular mesangial cells in culture express the kinin receptors and proliferate in response to bradykinin, suggesting that endogenous kinins and their receptors modulate glomerular growth. (4) The newborn period is characterized by an activation of kinin receptor gene expression, and chronic pharmacological blockade of kinin receptors suppresses DNA synthesis in the developing but not adult kidney. Collectively, these data provide the basis for the hypothesis that endogenous kinins and the kinin receptors play an important role in the developmental biology of the metanephric kidney.
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PMID:Development biology of the renal kallikrein-kinin system. 781 16

Angiotensin-converting enzyme or kininase II (ACE-KII) plays a central role in the control of circulating and tissue levels of angiotensin II and kinins. Both peptides have been implicated in the regulation of renal function and growth during normal development. We tested the hypothesis that the developing rat kidney expresses ACE-KII mRNA transcripts and the active enzyme and evaluated whether the developmental expression of the ACE-KII gene is related to changes in circulating angiotensin II and tissue kallikrein. ACE-KII mRNA and enzymatic activity were low in the newborn kidney; peak expression occurred on days 15 and 20 of postnatal life (16-fold versus day 1). In extrarenal tissues, ACE-KII activity and mRNA levels were also low during the newborn period in the following order of abundance: lung > kidney > aorta > heart. The lung showed a higher age-related increase in active ACE-KII and mRNA abundance (15-fold) than heart and aorta (activity, 3- to 4-fold; mRNA, 6- to 10-fold). The developmental profile of ACE-KII correlated temporally with changes in circulating angiotensin II and tissue kallikrein. Plasma angiotensin II levels were 2.5-fold higher in newborn than adult rats, whereas renal and extrarenal kallikrein-like activity increased twofold to fivefold from birth to adulthood. These results demonstrate that the ACE-KII gene is developmentally regulated in a tissue-specific manner. Tissue kinin generation and degradation, reflected by kallikrein and ACE-KII activities, are coordinately regulated during development, whereas circulating angiotensin II and tissue ACE-KII change in a reciprocal manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of somatic angiotensin-converting enzyme. 812 65

Phoneutria nigriventer venom was fractionated by gel filtration followed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those responsible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradykinin and histamine) were intradermally injected in male New Zealand white rabbits. Local oedema formation was measured as the local accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction XIII was the only fraction assayed which significantly induced oedema formation. Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk, whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that the increased vascular permeability induced by fraction XIII is due to local generation of kinins in response to tissue (but not plasma) kallikrein-kinin system activation.
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PMID:Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a fraction isolated from Phoneutria nigriventer (armed spider) venom. 831 Apr 40

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.
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PMID:Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy. 849 41

We investigated whether long-term infusion of kallikrein would attenuate renal injury in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. A subdepressor dose of purified rat urinary kallikrein (RUK) (700 ng/day) was infused intravenously by an osmotic minipump for 4 weeks in male Dahl S rats fed a high-salt (2% NaCl) diet. This dose did not affect the time-dependent elevation of blood pressure. However, urinary protein excretion was significantly decreased, and the glomerular filtration rate was increased. These beneficial effects were reflected morphologically by an attenuation of the glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl S rats. The kallikrein infusion increased the urinary excretion of bradykinin and stimulated the excretion of cyclic GMP, suggesting that the kallikrein-kinin-prostaglandin and nitric oxide axes were enhanced by the RUK infusion. The alterations induced by such infusion were potentiated by the concomitant administration of the angiotensin converting enzyme inhibitor alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl S rats, and this is probably mediated by an enhanced function of the kallikrein-kinin-prostaglandin and nitric oxide systems.
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PMID:Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive rats. 916 Jul 87

The kallikrein-kinin system (KKS) plays an important role in the regulation of renal function. Endogenous kinins modulate renal microvascular resistance, medullary blood flow, and distal nephron sodium and water reabsorption. All the components of the KKS, including tissue kallikrein, kininogen, kininase II, and kinin receptors are expressed within the kidney, establishing a paracrine system capable of controlling local nephron functions. In this review, data will be presented demonstrating that the developing kidney expresses an endogenous, functionally active KKS. Molecular studies have shown that gene expression of the renal KKS in the rat is activated postnatally, and that the intrarenal distribution of KKS components is subject to developmental control. Furthermore, the developmental expression of KKS appears to be regulated primarily at the transcriptional level. Ontogenetic studies have also revealed that the bradykinin B-2 receptor gene is overexpressed in the developing rat kidney. As kinins are potent vasoactive and growth-promoting factors, it is proposed that endogenous kinins mediate developmental renal growth and differentiation, and modulate the maturational changes which occur in renal hemodynamics.
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PMID:Ontogeny of the intrarenal kallikrein-kinin system: proposed role in renal development. 937 96

The kallikrein-kinin system (KKS) is involved in the regulation of blood pressure and in the sodium and water excretion. In humans, the KKS is divided functionally into a plasma KKS (pKKS) generating the biologically active peptide bradykinin and into the tissue (glandular) KKS (tKKS) generating the active peptide kallidin. The objective of this study was to examine the effect of a low-NaCl diet on the concentration of both pKKS and tKKS in plasma and urine in 10 healthy volunteers. After a 4-day low-NaCl diet, the urinary sodium and chloride excretions had decreased from 234 to 21.2 mmol/24 h and from 198 to 14.6 mmol/24 h, respectively. The plasma levels of ANG I, aldosterone, and angiotensin converting enzyme (ACE) significantly increased from 50.4 to 82.8 pg/ml, from 129 to 315 pg/ml, and from 46.4 to 59.8 U/ml, respectively, demonstrating the physiological adjustment to the low-salt diet. In plasma, the levels of bradykinin and plasma kallikrein had significantly decreased from 13.7 to 7.57 pg/ml and 14.4 to 7.13 U/ml, respectively. However, the levels of high-molecular-weight kininogen (HMW kininogen) remain unchanged (101 vs. 112 microg/ml, not significant). Contrary to plasma kallikrein, the plasma levels of tissue kallikrein increased (0.345 vs. 0.500 U/ml; P < 0.01). The plasma kallidin levels, however, did not change (64.7 vs. 68.6 pg/ml, not significant). This can be explained by a simultaneous decrease in the plasma low-molecular-weight kininogen (LMW kininogen) levels (89.9 vs. 44.4 microg/ml; P < 0.05). As in plasma, we find increased urinary concentrations of renal (tissue) kallikrein (23.3 to 42.8 U/24 h; P < 0.05) that contrast with, and are presumably counterbalanced by, urinary LMW kininogen levels (77.0 vs. 51.8 microg/24 h; P < 0.05). Consequently, in urine low-NaCl diet caused no significant change in either bradykinin or kallidin (9.2 vs. 10.8 microg/24 h, and 10.9 vs. 10.3 microg/24 h). It is concluded that the stimulation of the renin-angiotensin system on a low-NaCl diet is associated with a decrease in pKKS (bradykinin and plasma kallikrein) but not in tissue and renal KKS. Although tissue kallikrein is increased, there is no change in kallidin, as LMW kininogen in plasma and urine is decreased. These data suggest a difference in the regulation of pKKS and tKKS by low-salt diet.
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PMID:Low-salt diet downregulates plasma but not tissue kallikrein-kinin system. 968 9

The endothelial cell should be regarded as a highly active metabolic and endocrine organ interacting with the blood streak and the interstitium. Kinins are vasodepressor hormones that may participate in local blood flow regulation as part of an autocrine-paracrine system. We have previously reported that tissue kallikrein, its mRNA and kininogen are present in vascular tissue. The present study was undertaken to examine the release of the components of this system from isolated perfused rat vessels. These vessels were perfused at 4 ml/min with physiological saline solution containing 3% Ficoll and 0.1% BSA. Kallikrein was released into the perfusate at a rate of 75 +/- 5 ng Bk/100 g bw/30 min (n = 10). Kininogen was released at a rate of 55 +/- 5 pg Bk/100 g bw/30 min. Pre-treatment with puromycin, a protein synthesis inhibitor, significantly reduces kallikrein and kininogen release. Vascular derived kinins were released at a constant rate of 38 +/- 6 pg Bk/100 g bw/30 min for at least 120 min. This basal kinin release was increased 3-fold when perfused with the angiotensin converting enzyme inhibitor ramiprilat (p < 0.05). When purified kininogen was added to the physiological saline solution, immunoreactive kinins in the perfusate increased from 42 +/- 7 to 3140 +/- 210 pg Bk/100 g bw/30 min (n = 6; p < 0.002). Increase in flow rate (from 2 ml/min up to 4 ml/min and 8 ml/min) causes a parallel increase in the release of kinins (from 32 +/- 4 up to 48 +/- 6 and 62 +/- 8 pg Bk/100 g bw/30 min, respectively; p < 0.01); the increase may be due to the effect of shear stress upon the endothelial cells. The present data confirm that vascular tissue synthesizes and releases continuously kallikrein, kininogen and kinins. Vascular kinins induce potent vasodilatation through the release of prostacyclin, nitric oxide and endothelium-derived hyperpolarization factor, and some of the converting enzyme inhibitors effect may be explained by potentiation of vascular-derived kinins.
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PMID:Release of endothelial-derived kallikrein, kininogen and kinins. 983 May 4

1. Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws. 2. Up to 100 microg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method. 3. Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid. 4. Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not. 5. Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching. 6. Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin. 7. The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats. 8. These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent.
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PMID:Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists. 1005 Nov 36


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