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)

Experimental inflammation was induced by injection of a suspension of kaolin in carboxymethylcellulose solution into a subcutaneous air pouch preformed on the back of rats. Endogenous bradykinin generated in the inflammatory pouch declined quickly unless kininase inhibitors were administered into the pouch. Bradykinin injected into the pouch brought about no significant increase in plasma exudation in the pouch unless kininase inhibitors were administered simultaneously. Although kininase I and II activities were present in normal rat serum, kininase II rather than kininase I was mainly responsible for the degradation of bradykinin in rat serum. In the pouch challenged with the kaolin suspension and vehicle, kininase II originating from the pouch wall tissue played a predominant role in the degradation of bradykinin while the role of kininases derived from the blood and inflammatory cells was minor.
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PMID:Nature of kininase activity in the exudate in kaolin-induced inflammation of the air pouch type in rats. 284 64

Chick retina was screened for neuropeptide-metabolizing peptidase activity during development using a kininase bioassay in which hydrolysis of any peptide bond of bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) leads to inactivation, combined with chromatographic bradykinin-product analysis. Bradykinin was degraded at a high rate, 6.1-26.6 mU/mg protein, by retina homogenates of all developmental stages. Kininase activity increased 2.3-fold from the 8th to the 18th embryonic day and 2-fold in the immediate posthatching period relative to the activity level at hatching. Bradykinin-product analysis, 57-113% recovery of the peptide fragments, indicated that kininase activity corresponded mostly to endopeptidase A- and to endopeptidase B-like activities (hydrolysis of Phe5-Ser6 and Pro7-Phe8 peptide bonds, respectively) and to angiotensin I-converting enzyme activity at all developmental stages. The data indicated that the relative amounts of these activities vary during retina differentiation.
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PMID:Screening for neuropeptide-metabolizing peptidases during the differentiation of chick embryo retina. 299 15

We have studied the degradation of bradykinin, lysyl bradykinin and des-Arg9-bradykinin by the angiotensin converting enzyme. Bradykinin was cleaved at two sites to produce the pentapeptide Arg-Pro-Pro-Gly-Phe plus dipeptides Ser-Pro and Phe-Arg. Lysyl bradykinin was cleaved similarly to release the same dipeptides plus the hexapeptide Lys-Arg-Pro-Pro-Gly-Phe. The tripeptidase activity of ACE was observed when des-Arg9-bradykinin was digested. A single cleavage yielded the above pentapeptide plus Ser-Pro-Phe. Although des-Arg9-bradykinin was the most rapidly digested, when mixtures of des-Arg9-bradykinin and bradykinin or lysyl bradykinin were tested, virtually all of the bradykinin and most of the lysyl bradykinin was digested prior to the onset of digestion of des-Arg9-bradykinin. This was shown to be due to inhibition of des-Arg9-bradykinin cleavage by kinins and kinin-degradation products. The order in terms of potency was bradykinin greater than lysyl bradykinin greater than Ser-Pro much greater than Phe-Arg greater than Arg-Pro-Pro-Gly-Phe. The concentration of chloride ion was an important parameter which affected the rate of digestion of each substrate examined. des-Arg9-bradykinin was not digested by ACE in the absence of sodium chloride and the rate of digestion increased as the chloride concentration was increased to 100-150 mM. On the other hand, increasing NaCl concentration was inhibitory for bradykinin digestion. The rate of Lys-bradykinin digestion was increased from 0 to 1 mM NaCl and decreased thereafter up to physiologic concentration. A half-maximal rate was seen at 100-150 mM NaCl compared to no salt. Of the divalent cations examined, cupric ion inhibited further digestion of des-Arg9-bradykinin at physiologic concentrations. Our data indicate that the rate of degradation of kinins and the nature of the stable final cleavage products in plasma or serum (studied in vitro) are dependent upon the effects of chloride ion, metal ions, and the kinetic effects of multiple metabolites produced by at least two kininases.
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PMID:Studies of the digestion of bradykinin, Lys-bradykinin, and des-Arg9-bradykinin by angiotensin converting enzyme. 301 4

Bradykinin (BK) is widely believed to play a role in the pathogenesis of anaphylaxis. To help clarify any such roles, we examined for effects of inhibitors of kininase II (angiotensin converting enzyme, ACE) and "kininase I" (carboxypeptidase N, CPN), on the early course of egg albumin-induced aggregate anaphylaxis in anesthetized guinea pigs. In this model, pulmonary and systemic arterial blood pressure (BP) rise (unless pulmonary fibrillation occurs), lung wgt increases by approximately 60% and pulmonary microvessels are occluded by cell-rich thrombi, all within 5 min of i.v. antigen. The 30 min mortality rate is approximately 2%. ACE inhibitors (BPP9a, Captopril and MK 422; doses up to 140 mumol/kg) do not make anaphylaxis more nor less severe in terms discernible by changes in BP, lung wgt, EKG or intravascular coagulation. In marked contrast, an inhibitor of CPN (2-mercaptomethyl-3-guanidinoethylthiopropionic acid, 2-MGP; 8-16 mumol/kg) increases the 30 min mortality rate to 94% and lung wgt to 180% of control. The animals die in ventricular fibrillation. Given the enormous BK potentiating effects of BPP9a, Captopril and MK 422, it seems likely that little if any BK is formed in the early min of anaphylaxis. 2-MGP does not potentiate BP effects of BK but markedly potentiates effects of C3a anaphylatoxin. Thus, our data support the views that BK is neither a primary nor secondary mediator of aggregate anaphylaxis, and the adverse effects of 2-MGP are best explained in terms of preservation of anaphylatoxins and not in terms of preservation of kinins.
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PMID:Aggregate anaphylaxis and carboxypeptidase N. 302 62

Acute administration of captopril has been reported to decrease noradrenaline (NA) release from the sympathetic nerves. In this study the chronic effects of ramipril on the sympathetic nervous system of male spontaneously hypertensive rats (SHR) have been investigated and compared to those of captopril and enalapril. As parameters for catecholamine biosynthesis and storage, the activity of tyrosine hydroxylase and the catecholamine content of the hearts and the adrenal medulla were measured by HPLC in treated and control SHR. To assess sympathetic outflow plasma NA and adrenaline (A) levels were determined during preganglionic stimulation (PS) of the spinal cord. Under none of these drugs could differences be observed between the treated and control animals, neither in the biosynthesis and storage of catecholamines in the heart and adrenal medulla nor in the sympathetic outflow. However, the dose response curves of blood pressure vs PS were significantly shifted to the right when ACE-inhibitors were administered, most strongly by ramipril. In view of the unaltered presynaptic sympathetic function long term treatment with ACE-inhibitors is suggested to increase bradykinin and angiotensin I. Bradykinin and angiotensin I are capable of releasing NA and A from the adrenal medulla, like angiotensin II.
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PMID:Effects of chronic treatment with ramipril, a new ACE blocking agent, on presynaptic sympathetic nervous system of SHR. 303 97

Bradykinin infusion has been shown to improve glucose metabolism in non-insulin-dependent diabetic subjects (NIDD). Therefore, we tested the following hypothesis: inhibition of Kininase II, the bradykinin (BK) degrading enzyme, by captopril may also improve glucose metabolism in NIDD. Immediate effects of captopril on total body and peripheral glucose disposal were examined in five normotensive, normal weight NIDD and compared with five NIDD control subjects, well matched for age, weight and degree of fasting hyperglycaemia. The euglycaemic insulin clamp technique was employed in combination with the forearm catheter technique. After 90 min of insulin infusion a single dose of 25 mg captopril was administered orally, whereas in the control group a placebo was given. Captopril lead to a significant rise in total body glucose disposal and forearm glucose uptake, while in the control group no change was observed. Simultaneously, captopril lead to reduction in muscular release of lactate and pyruvate. We conclude that these results demonstrate the stimulatory effect of captopril on insulin-induced glucose disposal of the whole body, which appears to be a result of increased glucose utilization by peripheral tissues. Because of the described insulin-like activity of bradykinin, the concomitant accumulation of local kinins by captopril-induced inhibition of kininase II may represent an attractive hypothesis to explain the generated data sufficiently.
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PMID:Captopril enhances insulin responsiveness of forearm muscle tissue in non-insulin-dependent diabetes mellitus. 312 50

Neutral endopeptidase (NEP) (enkephalinase, EC 3.4.24.11) and angiotensin converting enzyme (ACE) are two peptidases that can cleave the C-terminal dipeptide bradykinin(8-9) from bradykinin. To determine whether these peptidases play roles in modulating kinin-induced contractions in the airways, we studied the effects of captopril, an ACE inhibitor, and of leucine-thiorphan and phosphoramidon, two NEP inhibitors, on the contractile responses to bradykinin and lysyl-bradykinin in isolated segments of ferret trachea. Bradykinin and lysyl-bradykinin-induced contractions in a concentration-dependent fashion (P less than .001), with a threshold of 10(-7) M and 5 x 10(-7) M, respectively. In contrast, the bradykinin(8-9) and the N-terminal heptapeptide bradykinin(1-7), the major fragments of hydrolysis of bradykinin by NEP and ACE, had a very weak or no effect on tracheal contraction in concentrations as great as 10(-5) M. Captopril, leucine-thiorphan and phosphoramidon (each inhibitor at 10(-5) M, 15 min) shifted the concentration-response curves to lower concentrations by approximately 1 to 1.5 log U (P less than .05). Both NEP inhibitors and the ACE inhibitor potentiated the response to bradykinin in a concentration-dependent fashion (P = .0001), and the combination of phosphoramidon and captopril resulted in an additive potentiation of bradykinin-induced contraction (P less than .02). [D-Pro2-D-Trp7,9]-substance P, a substance P antagonist, did not modify the potentiation of bradykinin-induced contraction by NEP inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutral endopeptidase and angiotensin converting enzyme inhibitors potentiate kinin-induced contraction of ferret trachea. 327 79

Rat liver cathepsin B was tested for its peptide-bond specificity against bradykinin and the oxidized insulin A-chain. Bradykinin was shown to be resistant to the action of cathepsin B. One possible reason for this resistance is the proline content of the peptide and the discrimination against proline residues at three or four subsites of cathepsin B. Oxidized insulin A-chain was degraded by a peptidyl dipeptidase activity. Three dipeptides were cleaved from the C-terminal part of the insulin A-chain after having been incubated for 2 h (molar ration E:S = 1:2800) and six dipeptides were released after a longer digestion (10 h, E:S = 1:575).
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PMID:Action of rat liver cathepsin B on bradykinin and on the oxidized insulin A-chain. 330 5

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.
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PMID:Role of bradykinin generating and degrading systems in the vascular permeability response induced with kaolin in rats. 332 Mar 43

Bradykinin, the end product of activation of the plasma contact system, may play a significant role in reactions to contrast material and in other forms of anaphylactoid and anaphylactic responses to drugs or antigens. Activation of factor XII initiates activity in the plasma contact system, and we have identified factors (negatively charged surfaces) present in elevated concentrations in the plasma of patients who are asthmatic or allergic that can "prime" their plasma for the initiation and/or potentiation of factor XII activation. In other studies, we have shown that persons who react to contrast material and persons who are asthmatic or allergic share both a potential for accelerated contact system activity and evidence of an increased mean concentration of low-level contact system products. Recently, we have found that contrast media can inhibit angiotensin-converting enzyme, the substance that hydrolyzes bradykinin and limits its systemic effects. Thus, a number of factors suggest that it is the potential for increased production of bradykinin in persons who are allergic or asthmatic that may account for the greatly increased susceptibility of these patients to contrast material. This susceptibility may be critically triggered by the contrast media-induced inhibition of angiotensin converting enzyme. In view of these findings, the possibility exists that most, if not all, significant reactions to contrast material require an underlying allergic diathesis that may, or may not, be apparent by history and conventional diagnostic testing.
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PMID:A coherent biochemical basis for increased reactivity to contrast material in allergic patients: a novel concept. 350 Jun 22


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