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)

Treatment of male guinea-pigs daily with an oral dose of 2 mg dehydroepiandrosterone (DHA) sulphate/100 g body weight for 2 weeks significantly reduced the glucose-6-phosphate dehydrogenase (G-6-PDH) activity of erythrocytes, liver, kidney and testis. Lactate dehydrogenase activity in plasma also decreased, but L-aspartate: 2-oxoglutarate aminotransferase (GOT) and L-alanine:2-oxoglutarate aminotransferase (GPT) activity in plasma remained unaffected. In liver and kidney, however, a significant rise in GOT and GPT was observed. A 2- to 3-7-fold increase of C19-steroids was observed in plasma, liver and kidney. In extracts of liver and kidney more than 60% of steroids were isolated from the sulphatide fraction. Only minor changes were detected in the metabolic pattern of C19-steroids, 17-hydroxysteroids prevailing in the free and sulphatide fractions, while 17-oxosteroids predominated in the sulphate and glucuronide fractions. A slight rise of cyclic AMP concentrations in liver and kidney tissue was attributed to the inhibition of phosphodiesterase by the DHA/G-6-PDH system
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PMID:Effects of exogenous dehydroepiandrosterone sulphate on various enzymes and on steroid metabolism in the guinea-pig. 13 7

When total DHEA, G-6-PDH activity, and c-AMP were determined in human neoplastic mammary tissue and corresponding normal tissue the G-6-PDH activity in the former tissue greatly exceeded that found in normal tissue. On the other hand, a remarkable decrease of total DHEA and c-AMP could be detected in cancer tissue, hinting at the participation of DHEA in the intracellular regulation of G-6-PDH and c-AMP levels.
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PMID:Interaction between dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and cyclic adenosine-3',5'-monophosphate in neoplastic and normal human mammary tissue. 17 67

The biochemical problems of psoriasis are discussed, especially two modern hypothesis about the pathogenesis of this skin disease. 1. DHEA-deficiency leading to an increase of G-6-PDH inaugurated by Holzmann et al. 2. cAMP deficiency in psoriatic lesions as a cause of psoriasis hypothized by Voorhees and Duell. A synopsis of the physiology of the steroid hormone DHEA (synthesis, regulation, conjugation and excretion) is given. There are doubts that this hypothesis is correct. Recent findings have indicated, that there is no decrease of cAMP in the psoriatic lesion--in contrast there is an increase of this cyclic nucleotid. It means that this theory is also doubtfull. Treatment of an hypothetical decrease of cAMP by AMP is not possible, because this AMP will not penetrate in the cell and cannot be metabolized to cAMP.
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PMID:[Psoriasis: A general disease? Can psoriasis be explained biochemically?]. 19 71

Experiments with rabbit platelets in vitro revealed differences in the effect of the aggregation inducers (ADP and thrombin) and the aggregation inhibitor cyclic AMP on the activity of the enzymes of pentosephosphate pathway of glucose oxidation. ADP and thrombin decrease significantly the activity of glucoso-6-phosphate dehydrogenase (G-6-PDH) and riboso-5-phosphate-metabolizing enzymes (R-5-PME) in platelets during aggregation, whereas cyclic AMP produces no appreciable effect on the G-6-PDH activity, but increases significantly the R-5-PME activity. ADP decreases and cyclic AMP raises substantially the activity of R-5-PME. The differences were also revealed in the effects produced by cyclic AMP and cyclic GMP on the enzymes of pentosephosphate pathway of glucose oxidation. Unlike cyclic AMP, cyclic GMP decreased significantly the activity of G-6-PDH. The activity of R-5-PME and cyclic GMP transketolase was more pronounced than that of cyclic AMP. Like cyclic AMP, cyclic GMP differs from ADP and thrombin in the action produced on the enzymes of pentosephosphate pathway of glucose oxidation.
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PMID:[Effect of aggregation inducers and inhibitors on the pentosephosphate pathway enzymes of glucose conversion in the thrombocytes]. 22 Dec 44

We have previously corroborated that lymphocyte beta-adrenergic receptor density is significantly reduced in patients with chronic heart failure. It is well known that angiotensin converting enzyme inhibitors normalize the function of sympathetic nervous system. We have assessed the effect of enalapril on lymphocyte beta-adrenergic receptor system from patients with chronic heart failure (n = 14) using a random, cross and double blind protocol. Our results show that the improvement in clinical score and ventricular function were not related with changes in the number and affinity of beta-adrenergic receptor nor cyclic AMP content in lymphocytes obtained from these patients.
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PMID:[Evaluation of the effect of enalapril, a converting enzyme inhibitor, on lymphocytic beta-adrenergic receptors of patients with chronic cardiac insufficiency]. 133 61

Previous studies on the possible antiarrhythmic effects of angiotensin converting enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or negative; however, proof of adequate ACE inhibition was not provided. Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL. Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01). Perindoprilat prevented the fall in the VFT and the increase in left ventricular end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure. Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group (both versus pre-CAL values). In the control group cyclic AMP was increased from 0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic zone of the perindoprilat group was increased, whereas blood flow in the central ischemic zone was decreased compared to the control group. However, levels of tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiarrhythmic effects of the angiotensin converting enzyme inhibitor perindoprilat in a pig model of acute regional myocardial ischemia. 138 73

In vitro data indicate that the activation of A2 adenosine receptors increases renin release by the accumulation of cyclic AMP. Because in human forearm vessels beta-adrenergic receptor stimulation causes the local release of renin and angiotensin II through the increase of cyclic AMP, we evaluated in six essential hypertensive subjects whether adenosine can release vascular angiotensin II. Adenosine was infused into the brachial artery at cumulatively increasing doses (0.5, 1.5, and 5 micrograms/100 ml forearm tissue per minute for 5 minutes each) during saline infusion and in the presence of the adenosine antagonist theophylline (100 micrograms/100 ml forearm tissue per minute for 15 minutes), while venous (ipsilateral deep forearm vein) and arterial (brachial artery) angiotensin II (picograms per milliliter) were measured at the end of each infusion period, and forearm angiotensin II net balance (picograms per minute) was calculated by venous-arterial differences corrected for forearm blood flow (strain-gauge venous plethysmography) and hematocrit. In control conditions, adenosine, at higher doses, caused a dose-dependent vasodilation and increased venous angiotensin II without affecting arterial values; therefore, the calculated angiotensin II net balance showed an adenosine-mediated dose-dependent release. Theophylline pretreatment blunted adenosine-mediated forearm blood flow increments and angiotensin II release. The local origin of angiotensin II was further confirmed in another group of six hypertensive subjects in whom the angiotensin converting enzyme inhibitor captopril, locally infused at the rate of 2.5 micrograms/100 ml forearm tissue per minute for 15 minutes, abolished the adenosine-mediated venous angiotensin II increments. Our data indicate that exogenous adenosine can stimulate the production of angiotensin II in the forearm vessels of hypertensive patients.
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PMID:Adenosine activates a vascular renin-angiotensin system in hypertensive subjects. 159 66

Pulmonary endothelial aminopeptidase P (AmP) may be an important contributor to the inactivation of circulating bradykinin in certain species. To examine this possibility, we measured AMP activity in vivo and in vitro using Arg-Pro-Pro-[3H]benzylamide (3H-APPB) as substrate under conditions of first order enzyme kinetics. Utilizing multiple indicator dilution techniques, metabolism of 3H-APPB to Arg and Pro-Pro-[3H]benzylamide by AmP was not detectable during a single transpulmonary passage in anesthetized rabbits (n = 4), cats (n = 3) and pigs (n = 4). However, percent metabolism of 3H-APPB ranged from 54 to 63% in anesthetized rats (n = 6). In all experiments, the substrate remained within the vascular space and was thus accessible to endothelial and blood AmP only. At the same time, single-pass transpulmonary percent metabolism of [14C]benzoyl-Ala-Gly-Pro by endothelial-bound angiotensin converting enzyme was remarkably similar among rabbits, cats, rats and pigs (60-65%). In culture, Vmax/Km of AmP was 3 to 10 x 10(-4) min-1 for human basal arterial and rabbit and bovine pulmonary arterial endothelial cell monolayers (2 x 10(5) cells). AmP activity in the supernatant of lung and kidney tissue (homogenized in saline containing 1-o-n-octyl-beta-glucopyranoside) from rabbit, cat, pig and rat expressed as Vmax/Km(min-1) per (g wet tissue/ml) was 0.74, 2.25, 3.91 and 185.8 (lung), and 1.0, 3.7, 8.4 and 438.3 (kidney), respectively. Similarly, Vmax/Km values of AmP in plasmas of cat, dog, rabbit, pig, calf (serum), human and rat were 0, 0.016, 0.025, 0.068, 0.191, 0.237 and 3.53 min-1. These results suggest that 1) there are large interspecies variations in AmP activities of plasma, lung and kidney; 2) of the species studied, the rat contains the largest activities of AmP; and 3) AmP appears to be located on the luminal surface of the rat pulmonary endothelium.
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PMID:Species variation in pulmonary endothelial aminopeptidase P activity. 176 77

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
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PMID:Inotropic effects of angiotensin II on human cardiac muscle in vitro. 224 22

The role of cyclic AMP in regulating the production of angiotensin converting enzyme (ACE) was investigated using cultured bovine aortic endothelial cells. Addition of dibutyryl cAMP [Bu)2cAMP) at 100 microM increased the ACE activity to 126% of control (P less than 0.005). This effect was blocked by either actinomycin D (0.1 microgram/ml) or cycloheximide (1.7 microM) indicating that RNA as well as protein synthesis was required for induction of the enzyme. After addition of (Bu)2cAMP, a lag period of 8 h was observed before increased ACE activity was detected. The stable analogues, 8-bromo cAMP (100 microM) and N6-monobutyryl cAMP (100 microM) also increased ACE activity but cAMP (100 microM) and O2-monobutyryl cAMP (100 microM) had no effect, in keeping with their susceptibility to phosphodiesterase in this system. Sodium butyrate (100 microM) was also inactive. The effect of (Bu)2cAMP on ACE was still observed in the presence of a maximal dose of dexamethasone, indicating that (Bu)2cAMP stimulates by mechanism(s) independent of the previously observed action of glucocorticoids on these cells. The phosphodiesterase inhibitor IBMX caused a dose-related increase in ACE activity with a threshold at 30 microM (P less than 0.05) and produced a 4-fold increase above control at 1 mM IBMX.
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PMID:Angiotensin converting enzyme induction by cyclic AMP and analogues in cultured endothelial cells. 244 4


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