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

---

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

We investigated how bradykinin mediates inflammatory reactions in rats, via measurements of bradykinin by enzyme immunoassay method in inflammatory tissue fluids. Vascular permeability was increased markedly during the first 10 min and then declined quickly after the infusion of a kaolin suspension (10 mg/ml) in 0.8% carboxymethl-cellulose solution into an air pouch formed on the back of rats. Bradykinin in the exudate reached a maximum 5 min after the challenge and then decreased quickly. Local treatment with DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, an inhibitor of kininase I, and captopril, an inhibitor of kininase II in the first 10-min period, each enhanced the vascular permeability increase accompanied by the elevation of the bradykinin level, whereas soybean trypsin inhibitor, a plasma kallikrein inhibitor, lowered both vascular permeability and bradykinin. When applied in the period of 3.5 to 4 hr after the challenge, only the kininase II inhibitor was effective in elevating both vascular permeability and the bradykinin level, whereas soybean trypsin inhibitor was ineffective on vascular permeability. A bradykinin-degrading activity appeared in the exudate as early as 10 min after the challenge. These results suggest that bradykinin plays an essential role for the sudden rise of the vascular permeability observed immediately after the infusion of kaolin suspension. In the later stage (3.5-4 hr), bradykinin level remained below the assay limit of 0.07 ng/ml in spite of its active generation, presumably because of its rapid degradation by the kininases, although it still played a definite role in the vascular permeability increase.
...
PMID:Role of bradykinin generating and degrading systems in the vascular permeability response induced with kaolin in rats. 332 Mar 43

Although kinins have been reported to affect cerebral vascular tone and permeability, their actions are not potentiated by angiotensin converting enzyme inhibitors. To investigate cerebral vascular kinin metabolism, porcine cerebral microvessels were isolated by differential sieving and centrifugation and characterized by microscopic examination and marker enzyme enrichment. Purified microvessels contained a membrane-bound carboxypeptidase which hydrolyzed the C-terminal Phe-Arg bond of both kallidin and bradykinin. Hydrolysis was optimal at pH 7.0, was activated more than 300% by 0.1 mM CoCl2, and was inhibited by o-phenanthroline and the carboxypeptidase N (EC 3.4.17.3) inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGETPA) (IC50 = 2 microM). Conversely, inhibitors of angiotensin I converting enzyme (captopril), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme (Z-Pro-prolinal), dipeptidyl(amino)peptidase IV (diprotin A) and amino-peptidase M (amastatin) had no effect. When the rates of C-terminal hydrolysis of kallidin by detergent-solubilized cerebral microvasculature were determined over a range of substrate concentrations (16.6 to 250 microM), the Km and Vmax values obtained were 26.0 +/- 3.0 microM and 14.7 +/- 1.3 nmol/min/ml (N = 4) respectively. These data suggest that a cerebral microvascular carboxypeptidase may play a role in vivo in modulating the effects of kinins on cerebral blood flow and permeability and in preventing circulating kinins from crossing the blood-brain barrier.
...
PMID:Kallidin and bradykinin metabolism by isolated cerebral microvessels. 339 72

We have compared the digestion of bradykinin, lysyl bradykinin, and kinin degradation products by carboxypeptidases N, B and A (CPN, CPB and CPA). Carboxypeptidase N removed the C-terminal arginine from bradykinin or lysyl bradykinin to leave the des-Arg derivative of each, and no further degradation occurred regardless of enzyme concentration or time of incubation. However, both CPB and CPA degraded the des-Arg derivatives to remove the C-terminal phenylalanine. The inhibitory effect of phosphate ions upon this activity of CPB (but not CPA) suggests that CPA may be responsible for the formation of free phenylalanine seen upon degradation of kinins in plasma or serum. However, angiotensin converting enzyme degraded des-Arg9-bradykinin in plasma or serum prior to such Phe removal to yield the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We demonstrated that CPB degraded Arg-Pro-Pro-Gly-Phe but not Ser-Pro-Phe; this reaction was also inhibited by phosphate ions. Carboxypeptidase A, on the other hand, liberated Phe from both peptides in phosphate-buffered saline and accounted, at least in part, for the free phenylalanine detected. Carboxypeptidase N did not digest the aforementioned pentapeptide or tripeptide. It is clear that carboxypeptidase B and carboxypeptidase A had overlapping activities, depending upon the substrate tested, and were distinguished by the effects of different ionic environments. We further suggest a role for carboxypeptidases other than CPN in the degradation of kinins in human plasma or serum.
...
PMID:Studies of the digestion of bradykinin, lysyl bradykinin, and kinin-degradation products by carboxypeptidases A, B, and N. 371 39

In order to investigate the role of the renal kallikrein-kinin (K-K) system in normal (NRH) and low renin (LRH) subgroups of essential hypertension (EHT), daily excretions of urinary kallikrein (KAL) quantity and activity, kinin (KIN), total and pre-KAL, and kininase I and II were measured in 21 normotensives (NT), 29 patients with NRH and 16 patients with LRH. The daily excretions of both KAL quantity and activity, total and pre-KAL, and KIN were significantly lower in NRH and LRH than in NT. That of kininase I was significantly higher in NRH and LRH than in NT, but that of kininase II was not. In comparing NRH and LRH, the urinary excretions of KAL activity and KIN were lower in LRH than in NRH, and that of kininase I was higher in LRH than in NRH. The KAL/total KAL ratio did not show any significant difference among NT, NRH and LRH. These findings suggest that the suppression of the renal K-K system in EHT seems to be due to both the decrease of KAL through the pre-KAL synthesis in the kidney and an increase of kininase I activity, but not to the inhibition of conversion from pre-KAL to active KAL and the more obvious suppression of this system in LRH than in NRH may be partly explained by KAL inhibitors and/or increased kininase I activity.
...
PMID:Study on the renal kallikrein-kinin system in normal and low renin subgroups of essential hypertension. 610 Jul 42

We have utilized several inhibitors to assess the effects of kininases on the contractile activity of bradykinin (BK), kallidin (KD), des-Arg9-BK and des-Arg10-KD on two isolated blood vessels, the rabbit aorta and mesenteric vein. The response of the two vessels to kinins are mediated by B1-receptors, implying that fragments of kinins without the C-terminal arginine are much more active on these tissues than the whole kinin sequences. Blockers of carboxypeptidase B-like enzymes, such as SQ24798 and pivalyl-L-arginine decrease the apparent affinity of BK and KD on the two vessels, while not changing those of des-Arg9-BK and des-Arg10-KD; this suggests that a major part of the contractile activities of BK and KD are mediated by des-Arg metabolites formed in situ at the tissue level by a kininase I. The block of kininase II by captopril or desacetylated MK-421 bring about a complex pattern of activity changes that include the potentiation of BK and KD and the depression of des-Arg10-KD. These results, in conjunction with those obtained with the non-specific inhibitors of metallopeptidases, thioglycolic acid and EDTA, suggest that the relative contribution of kininase I and kininase II to the degradation of kinins in arterial and venous vessels may be different. The implications of these findings on the pharmacology of B1-receptors are discussed.
...
PMID:Kininases and vascular responses to kinins. 612 86

Carrageenan-induced edema of rat paw was greatly potentiated by orally or locally administered angiotensin converting enzyme (CE, identical with kininase II) inhibitor, (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (YS980). The potentiative effect of YS980 was observed by the administration not only prior to but also 3 hr after the carrageenan injection. The vascular permeability test showed the same potentiative effect of YS980 in the inflamed tissue of carrageenan edema. Bradykinin potentiating peptide-B (BPP-B) and 1,10-phenanthroline also potentiated the edema and the effects of these compounds were in order of YS980 greater than BPP-B greater than 1,10-phenanthroline. The order was in accordance with that of inhibitory potencies against kininase II activity of rat serum in vitro. However, the activity of kininase I was not affected by YS980 and BPP-B. In addition, among various experimental models of acute paw edema, the potentiative effects of YS980 were restricted to the inflammations mediated by kinins such as carrageenan, cellulose sulfate, kaolin and bradykinin-induced edema. These results suggest that the potentiative effect of YS980 on carrageenan edema is mainly based on its inhibitory effect on kininase II in the inflamed site.
...
PMID:[Potentiative effects of angiotensin converting enzyme inhibitors on carrageenan-induced edema in rats]. 629 82

Bradykinin (BK) and [des-Arg9]-bradykinin (-9BK) concentrations in blood and urine samples from 18 normotensive subjects and 23 patients with low-renin essential hypertension were determined by radioimmunoassay. BK and -9BK levels in venous blood from normotensive subjects were 67.1 +/- 60.8 pg/ml and 204.1 +/- 44.5 (mean +/- S.D.), respectively, and levels in urine from normotensive subjects were 5.3 +/- 5.3 ng/ml and 1.6 +/- 1.2, respectively. The blood and urinary levels of BK and -9BK in low-renin essential hypertensives were not significantly different from those of normotensives and did not change when the hypertensives were treated with the new orally active angiotensin I-converting enzyme (ACE) inhibitor, enalapril (MK421). It has been proposed that BK levels do not change with ACE inhibition because under these conditions BK might be metabolized to -9BK by kininase I. Since -9BK levels did not increase with MK421 treatment, this possibility can be excluded. The absence of elevations in blood and urine BK and -9BK after administration of MK421 does not support an involvement of kinins in the mechanism of antihypertensive action of MK421 in these patients. On the basis of the data, it is not possible to exclude such an involvement, however, because local changes in kinin concentrations could occur that are not reflected by changes in circulating or urinary kinin levels.
...
PMID:Immunoreactive bradykinin and [des-Arg9]-bradykinin in low-renin essential hypertension--before and after treatment with enalapril (MK 421). 631 33

Several enzymes, enzyme inhibitors, receptors and transport structures are situated on the luminal surface of endothelium. Some enzymes and transport systems are continuously active and, in effect, regulate the composition of blood moving downstream. Other components are latent. Their activities are not expressed in the absence of stimulus. Thus, endothelial cells injured by granulocytes or viral infection possess receptors for the Fc segment of IgG and for C3b, whereas normal endothelial cells do not. Both normal and injured endothelial cells express receptors for Clq. To visualize surface enzymes, inhibitors, receptors and transport structures, we have prepared surface replicas suitable for high resolution EM. The surface replication technique, coupled with immunocytochemical procedures, facilitates studies of the topographies of surface enzymes such as angiotensin converting enzyme (ACE) and carboxypeptidase N (CPN). In addition, the replicas provide unique views of the glycocalyx, a cell coating previously believed to be amorphous but now seen to be a highly organized carpet-work under which surface enzymes, receptors, etc are embedded. Given its content of fibronectin, the glycocalyx may be the Clq receptor. Cells treated with antibodies to ACE or CPN show disarrayed glycocalyces and bind Fc and C3b. Latency of the Fc and C3b receptors may be owing to the physical barrier provided by the glycocalyx. Apparently, damage to the glycocalyx creates conditions favoring binding of immune complexes, complement activation and intravascular coagulation with loss of gradients between blood and parenchyma. Whether some non-thrombogenic properties of endothelium require an intact glycocalyx deserves consideration as does the role of the glycocalyx in regulating microvascular permeability.
...
PMID:The ultrastructural basis of endothelial cell surface functions. 646 85

The carboxypeptidase N and angiotensin converting enzyme contents was 1.4-1.5-fold higher in emotionally stable rats as compared with those predisposed to an emotional stress. Possible causes of this phenomenon are discussed.
...
PMID:[Carboxypeptidase N and angiotensin-converting enzyme activities in the blood serum of rats with different resistances to emotional stress]. 753 82

Bradykinin (BK) and its fragments BK(1-8), BK(1-7), and BK(1-5) were incubated with sheep nasal homogenates to investigate the extent of peptide metabolism within the nasal mucosa. The products for both bradykinin and BK(1-8) degradation were found to be BK(1-7) and BK(1-5). BK(1-7) was metabolized to BK(1-5) alone. The patterns of degradation suggest that the Pro7-Phe8 bond of bradykinin was hydrolyzed first, then BK(1-7) was further hydrolyzed to form BK(1-5). The metabolism of bradykinin in rat nasal homogenates and plasma was also investigated. BK(1-5) was the only metabolite measurable in the rat nasal homogenates, likely due to the activity of an endopeptidase. The reduction in the bradykinin degradation rate resulting from the inhibition of angiotensin converting enzyme (ACE) or carboxypeptidase N indicates that these enzymes participate in mucosal bradykinin metabolism to some degree. In comparison, the products of bradykinin hydrolysis in rat plasma were found to be BK(1-8), BK(1-7), and BK(1-5). These results indicate that the enzyme populations or/and activities vary significantly between different species and between different tissues within the same species. Although significant aminopeptidase activities were detected in the sheep nasal homogenates, bradykinin was not affected by their presence, since the N-terminal sequence of bradykinin is not susceptible to hydrolysis by most aminopeptidases.
...
PMID:Presystemic bradykinin metabolism in sheep and rat nasal homogenates. 756 26


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---