Angiotensin‐converting Enzyme (Ace) Measurement in Human Serum Using Radioinhibitor Ligand Binding

Jackson, Bruce; Cubela, Rose; Johnston, C. I.

doi:10.1038/icb.1986.16

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…This radioiodinated compound could also be used to study the in vivo distribution of APN in various parts of the body after systemic administration, as already shown for NEP (Sales et al, 1991). Finally, the possibility to follow directly by competition the bioavailability of selective or dual NEP/APN inhibitors administered by di¡erent routes as already shown in the case of NEP and angiotensin converting enzyme (Fournië-Zaluski et al, 1994;Jackson et al, 1986) is important considering the potential clinical application of these molecules (review in Roques et al, 1993).…”

Section: Discussionmentioning

confidence: 97%

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

et al. 2001

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The selective and potent aminopeptidase N inhibitor [125I]RB 129 has been used for the radioautographic localization of this enzyme in rat brain, spinal cord and intestine. Brain microvessels and intestine brush-border cells were shown to present a high concentration of aminopeptidase N. Moreover, a labeling of various brain structures was observed. A very high level of binding occurred in the meninges, choroid plexus, pineal gland, paraventricular nucleus and pituitary gland. Moderate to high labeling was also observed in the cortex, caudate-putamen, subthalamic nucleus, central periaqueductal gray, thalamus, as well as in the dorsal and ventral horn of the spinal cord, which are known to contain a high concentration of enkephalins, opioid receptors and neutral endopeptidase. This co-localization confirms the physiological implication of aminopeptidase N in the inactivation of enkephalins accounting for the requirement of dual inhibition of neutral endopeptidase and aminopeptidase N to observe highly significant morphine-like effects induced by the protected endogenous opioid peptides. Aminopeptidase N was also visualized in moderate to high levels in other brain structures such as the hippocampus, nucleus accumbens, substantia nigra, hypothalamus (dorsomedial and ventromedial nuclei), raphe nucleus, pontine nucleus, inferior olive, and in high concentration in the granular layer of cerebellum. In summary, aminopeptidase N has been visualized for the first time in numerous brain areas using the selective inhibitor [125I]RB 129. This iodinated probe could allow the ex vivo and in vivo localization of aminopeptidase N in various tissues to be investigated and may also be used to evaluate quantitative changes in aminopeptidase N expression in pathological situations. Aminopeptidase N, which preferably removes NH2-terminal neutral amino acids from peptides, has probably a host of substrates. Nevertheless, a certain in vivo selectivity could be achieved by the presence of the enzyme in structures where the peptide effector and its receptors are also co-localized.

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Section: Discussionmentioning

confidence: 97%

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

et al. 2001

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“…Jackson et al 91 been prepared. Alhenc-Gelas et al 93 proposed a direct RIA for the measurement of human ACE level.…”

Section: B Methods Measuring the Ace Moleculementioning

confidence: 99%

Angiotensin-Converting Enzyme: Clinical Applications and Laboratory Investigations on Serum and Other Biological Fluids

Bénéteau-Burnat

Baudin

1991

Critical Reviews in Clinical Laboratory Sciences

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Angiotensin I-converting enzyme (ACE) is a peptidyldipeptide hydrolase that is located mainly on the luminal surface of vascular endothelial cells but also in cells derived from the monocyte-macrophage system. Physiologically, ACE is a key enzyme in the renin-angiotensin system, converting angiotensin I into the potent vasopressor angiotensin II and also inactivating the vasodilator bradykinin. Increased serum ACE activity (SACE) has been reported in pathologies involving a stimulation of the monocytic cell line, primarily granulomatous diseases. Sarcoidosis is the most frequent and the better studied of these diseases; high SACE is not only a well-established marker for the diagnosis but is also a useful tool for following its course and evaluating the effect of therapy. SACE can also be increased in nonsarcoidotic pulmonary granulomatous diseases such as silicosis and asbestosis, in extrathoracic granulomatous pathologies such as Gauchers disease and leprosis, and, to a lesser extent, in nongranulomatous disorders such as hyperthyroidism or cholestasis. On the other hand, monitoring sarcoidosis obviates the measurement of ACE activity in other biological fluids, e.g., broncho-alveolar and cerebrospinal fluids, in the search of a locoregional dissemination or dis-simulation of the disease. Decreased SACE has been reported in vascular pathologies involving an endothelial abnormality, e.g., deep vein thrombosis, and in endothelium dysfunctions related to the toxicity of chemo- and radiotherapy used in cancers, leukemias, and hematopoietic or organ transplantations. SACE is also of interest for monitoring arterial hypertension treated with specific synthetic ACE inhibitors. These various reasons for determining ACE activity have led to the development of numerous methods. The most widely used is the spectrophotometric assay using hippuryl-histidyl-leucine as substrate. Fluorimetric and radiochemical assays using both classic and novel substrates have been proposed, but they are time consuming, require special apparatus, and are not suited to automation. Kinetic spectrophotometry of furylacryloyl-phenylalanyl-glycyl-glycine hydrolysis is now used extensively because it is easy to automatize. Efforts are now required to standardize one or more of these assays. Indeed, "normal" plasma values differ not only according to the substrate, but also to the method of determination and to sex and age.

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“…The chloramine T method was used to iodinate 351A (Hunter & Greenwood 1962) and free I z 5 I was separated from Iz51-351A by passage over a SP Sephadex C25 column (Hichens et al 1981). The radioligand has been shown to be stable on incubation with tissues (Jackson et al 1986a) and to bind in a competitive manner to ACE in plasma and tissues, in proportion to the ACE content (Jackson et al 1986b). Scatchard analysis of binding in rat serum and tissues has yielded a straight line, suggesting a single specific binding site.…”

Section: Introductionmentioning

confidence: 98%

“…lZ5I-351A bound to ACE was separated from unbound 12sI-351A by alcohol precipitation. Optimal binding conditions have been established previously (Jackson et al 1986b). Incubation buffer of 0.05 mol/l tris buffer (pH 7.0) contained 0.3% bovine serum albumin, 75 mmol/l NaCl, and 50 pmol/l ZnSO, Tissue ACE was prepared from whole organs, which were diced rapidly at 4°C then homogenized in assay buffer for 20 s, centrifuged (15 min, 4"C, 1800 g), the pellet resuspended in assay buffer and recentrifuged.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Angiotensin Converting Enzyme Inhibition in Tissues Following Oral Lisinopril: Studies in the Rat Using Quantitative Radioinhibitor Binding

Jackson

Cubela

Sakaguchi

et al. 1987

Clin Exp Pharma Physio

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1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in plasma and tissues were measured in the rat following 10 mg/kg lisinopril given by oral gavage. 2. Specific binding of 125I-351A to ACE was measured in plasma, and homogenates of lung, aorta, kidney, testis, epididymis and brain, and used as an index of ACE activity. 3. Plasma ACE binding of 125I-351A was reduced to 5% of that in untreated rats 2 h after treatment, and returned to normal by 48 h. Kidney ACE showed a similar time course. Angiotensin converting enzyme from lung, aorta and brain was inhibited at a slower rate, and to a lesser degree. No significant inhibition of ACE was detected in epididymis or testis. 4. Individual tissues in the rat had differences in time course and degree of ACE inhibition after a single dose of lisinopril.

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Angiotensin‐converting Enzyme (Ace) Measurement in Human Serum Using Radioinhibitor Ligand Binding

Cited by 12 publications

References 17 publications

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

Angiotensin-Converting Enzyme: Clinical Applications and Laboratory Investigations on Serum and Other Biological Fluids

Pharmacokinetics of Angiotensin Converting Enzyme Inhibition in Tissues Following Oral Lisinopril: Studies in the Rat Using Quantitative Radioinhibitor Binding

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