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)

1 The vascular bed of the tongue in situ was perfused with blood through the lingual arteries at a constant pressure in anaesthetized dogs. All drugs except for SQ 14,225 were administered intra-arterially.2 Prostaglandin F(2alpha) (PGF(2alpha)) produced a dose-dependent increase in blood flow through the lingual arteries (vasodilatation).3 Marked desensitization was observed on the vasodilator responses to repeated administration of PGF(2alpha).4 The vasodilator response to PGF(2alpha) was abolished by tetrodotoxin in doses that abolished the vasodilator response to electrical stimulation of the lingual nerve.5 The vasodilator response to PGF(2alpha) was not affected by hexamethonium in doses that almost abolished the vasodilator response to lingual nerve stimulation.6 The vasodilator responses to PGF(2alpha) and to lingual nerve stimulation were scarcely modified by (-)-hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine.7 Electrical stimulation of the vago-sympathetic trunk and noradrenaline produced a decrease in blood flow through the lingual arteries.8 These results indicate that the vasodilator response of the tongue to PGF(2alpha) is due exclusively to excitation of parasympathetic postganglionic neurones and that neuronal receptors involved are quite distinct from nicotinic receptors.9 Intravenous administration of SQ 14,225, an inhibitor of angiotensin I converting enzyme or kininase II, augmented the vasodilator responses to bradykinin and kallikrein but not that to lingual nerve stimulation.10 The results suggest that neither kallikrein nor*kinin (including bradykinin) is responsible for the parasympathetically induced vasodilatation in the tongue.
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PMID:Vasodilatation by prostaglandin F2alpha in the canine tongue through a parasympathetic mechanism. 66 1

Kinins and prostaglandins of the E series (PGE) have the capacity to influence renal hemodynamic and excretory events and may interact intrarenally so as to reinforce one another. Thus, in the isolated Krebs-perfused rabbit kidney we showed that addition of either bradykinin or kininogen to the perfusing fluid augments the release of a PGE-like substance and that aprotinin, a kallikrein inhibitor, reduces the release of prostaglandins evoked by kininogen but not by bradykinin. Moreover, we have observed that deoxycorticosterone, an agent which increases urinary kallikrein, enhances the urinary excretion of PGE-like substance, and that this effect is prevented by simultaneous treatment with aprotinin. These observations and our demonstration that enhanced intrarenal activity of the kallikrein-kinin system, consequent to kininase II inhibition, is associated with renal vasodilation, diuresis, and natriuresis, suggest that a coupling of kinins and prostaglandins intrarenally may be directed towards the facilitation of salt-water excretion. The interdigitation of prostaglandins and the kallikrein-kinin system may thereby constitute the essential operation of a regulatory system in which the complementary actions of these hormones antagonize the sodium retaining effect of mineralocorticoids in those states in which salt-water balance is positive.
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PMID:Interaction of mineralocorticoids, renal prostaglandins and the renal kallikrein-kinin system. 76 63

The activity of carboxypeptidase A [EC 3.4.12.2] was inhibited by 3-phenylpropionate derivatives (p-aminocinnamate, 3-p-aminophenylpropionate and 3-p-acetylaminophenylpropionate), and to investigate its use as a ligand for affinity chromatography 3-p-aminophenylpropionate was directely and indirectly coupled to Sepharose 4B. carboxypeptidase A was adsorbed only on 3-p-aminophenylpropionate bound to the gel through p-phenylenediamine as a spacer. Carboxypeptidase A from pancreas was purified by a combination of this affinity adsorbent and ion exchange chromatography. The purified carboxypeptidase A had a homogeneity similar to that of a commercial product, as judged by disc gel electrophoresis. The carboxypeptidase activity of Pronase was slightly retarded on the gel column, but could not be separated from its caseinolytic activity. Angiotensin I-converting enzyme [peptidyl dipeptidy hydrolase, EC 3.4.15.1] obtained from hog kidney cortex was not bound to the gel.
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PMID:Purification of carboxypeptidase A using Sepharose 4B-bound 3-phenylpropionate. 89 53

Polymerase chain amplification experiments indicate that the germinal specific promoter of the angiotensin I-converting enzyme (ACE) is completely extinguished in somatic tissues. Despite this very strict specificity of expression, the germinal ACE promoter is active in transient transfection experiments in two somatic cell lines and one cell line of germinal origin. The analysis of the promoter shows the existence two regulatory elements within the first 350 bp: a proximal positive element and a distal negative element.
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PMID:Functional study of the germinal angiotensin I-converting enzyme promoter. 128 Apr 15

1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum.
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PMID:A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder. 128 72

Protein sequencing and molecular cloning of human endothelial angiotensin I-converting enzyme (ACE; kininase II), have led to a description of the structure of the enzyme and to several questions concerning the intracellular maturation of ACE and the mechanisms of enzyme action. With the help of recombinant ACE expression in mammalian cells and site-directed mutagenesis, a model for the maturation of ACE in endothelial cells has been proposed. This model comprises transmembrane anchoring of the membrane-bound ACE near its carboxyterminal extremity, and post-translational cleavage of the anchor in the secreted form. The endothelial ACE displays a high degree of internal homology between two large peptidic domains that each bears a consensus sequence for zinc binding and therefore a putative active site. The testicular ACE, however, encoded from the same gene by a shorter mRNA, contains only the carboxyterminal half of endothelial ACE and therefore a single active site. Expression of ACE mutants with only one intact homologous domain, however, indicates that in endothelial ACE both domains are enzymatically active. Further characterization of these two active sites of endothelial ACE is in progress. In humans, population studies have indicated that the large interindividual variability in plasma ACE levels is partly genetically determined and under the influence of a major gene effect. This was later confirmed and extended by the observation of an insertion-deletion polymorphism of the ACE gene that is associated with the level of ACE in plasma. The clinical implications of these observations are discussed.
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PMID:The angiotensin I-converting enzyme (kininase II): molecular organization and regulation of its expression in humans. 128 23

The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA.
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PMID:Bradykinin degrading activity in cultured human endothelial cells. 128 24

Because converting enzyme and kininase II are identical enzymes and probably influence both the biosynthesis of angiotensin II and the metabolism of bradykinin, we investigated the effects of bradykinin and desArg-bradykinin on the sympathetic outflow of pithed spontaneously hypertensive rats (SHRs) before and after acute or chronic inhibition of the converting enzyme by ramipril. Sympathetic outflow was induced by preganglionic electrical stimulation of the spinal cord and measured as circulating, stimulation dependent norepinephrine and epinephrine by high-performance liquid chromatography (HPLC) and electrochemical detection. Bradykinin increased dose-dependently norepinephrine and epinephrine release, particularly when converting enzyme was inhibited. DesArg-bradykinin did not influence norepinephrine outflow but caused a dose-dependent increase in epinephrine release only after converting-enzyme inhibition. It is suggested that both bradykinin and desArg-bradykinin could compensate for the lack of effect of angiotensin II on sympathetic outflow.
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PMID:Changes in peripheral sympathetic outflow of pithed spontaneously hypertensive rats after bradykinin and DesArg-bradykinin infusions: influence of converting-enzyme inhibition. 128 27

Angiotensin-converting enzyme (ACE) inhibitors exert their beneficial effects not only via endocrine mechanisms, but most probably also via interference with autocrine-paracrine actions involving local renin-angiotensin and kallikrein-kinin systems with subsequent autacoid release. Inhibition of ACE (kininase II) results in the reduction of angiotensin II generation and kinin degradation, leading to beneficial cardiovascular effects. Bradykinin and prostacyclin release from isolated rat hearts was increased by local ACE inhibitions with ramiprilat. In different models the bradykinin-mediated effects of ACE inhibition were abolished with the specific B2 kinin-receptor antagonist Hoe 140: The cardioprotective effects of ramiprilat or ramipril such as reduction of postischemic reperfusion injuries in isolated rat hearts or the reduction in infarct size in dogs and rabbits were abolished by coadministration of Hoe 140. Furthermore, left ventricular hypertrophy in rats with aortic banding could be prevented or regression was induced when the ACE inhibitor was given in a non-blood pressure-lowering dose. These beneficial effects were also abolished by Hoe 140. In conclusion, in different experimental models, ACE inhibitors exert cardioprotective effects. An enhancement of endothelial autacoid formation (nitric oxide and prostacyclin) by inhibiting degradation of bradykinin may contribute to these effects.
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PMID:Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. 128 35

We studied the effects of the estrous cycle, ovariectomy and estrogen replacement on angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) and angiotensin II (AT) receptors in the pituitary gland of the female rat. Quantitative autoradiography, with the use of consecutive pituitary sections, allowed for simultaneous determination of changes in binding and in the potential AT synthetic ability of individual pituitaries, and for a correlation between these two phenomena. In the anterior pituitary, ACE activity and binding of the ACE inhibitor [125I]-351A were not changed during the estrous cycle. Ovariectomy produced a significant increase in ACE activity and binding, and both of these parameters returned to normal after estrogen replacement. There were no changes in ACE activity or binding in the posterior pituitary during the estrous cycle or after ovariectomy or hormone replacement. AT receptors were characterized as of the AT1 type, since they were displaced by the selective AT1 antagonist DuP 753 and not by the AT2 competitor PD 123177. There were marked changes in the concentration of AT1 receptors during the estrous cycle, with highest numbers in metestrus, lower in estrus and diestrus, and lowest during proestrus. Estrogen replacement in ovariectomized rats decreased AT1 receptor number in the anterior pituitary. Our results indicate a dual effect of estrogen on anterior pituitary AT, physiologically on AT receptor expression and pharmacologically on ACE activity.
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PMID:Estrogens regulate angiotensin-converting enzyme and angiotensin receptors in female rat anterior pituitary. 131 39


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