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Biomedical subjects

T Unger

Publications and source records attributed to T Unger.

At least 379 records · Page 21Linked to original sources
PubMed1980

Components of the renin-angiotensin system in the cerebrospinal fluid of rats and dogs with special consideration of the origin and the fate of angiotensin II.

From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotension II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.

Angiotensin I↗
PubMed1980

Hydrolysis of some cystine amniopeptidase and aminopeptidase substrates by human placental enzymes after isoelectric focusing.

Several cystine aminopeptidase- and aminopeptidaselike activities of mature human placenta were demonstrated by chromatography on CM-Sephadex and subsequent preparative flat bed isoelectric focusing. Enzyme tests were carried out by using a micro modification of the Bratton-Marshall reaction with seven amino acid-rho-nitroanilides and one amino acid beta-naphthylamide as substrates. By this method three main activities were detected; each was nonhomogeneous and capable of hydrolyzing cystine aminopeptidase- as well as aminopeptidase substrates. The substrates benzyl-cystine-rho-nitroanilide, cystine di-rho-nitro-anilide and cystine di-beta-naphthylamide were split by different enzymes. By studying the effects of several effectors or of heating, no enzyme with the properties described in the literature for serum cystine aminopeptidase could be unequivocally demonstrated. The results report here suggest that serum cystine aminopeptidase--in contrast to placenta cystine aminopeptidase--is either altered severely in its structure or that it represents a multiplicity of enzymes, which attack "specific" substrates and are therefore jointly manifested as cystine aminopeptidase.

Aminopeptidases↗
PubMed1979

Purification and properties of a collagen peptidase (PZ-peptidase) from rabbit serum.

A peptidase cleaving a synthetic substrate for collagen peptidases, 4-phenylazobenzyloxcarbonyl-L-Pro-L-Leu-Gly-L-pro-D-Arg (designated as PZ-peptide) has been purified 1200-fold from rabbit serum and characterized. The enzyme preparation is free of collagenase and unspecific proteinase activity. The natural substrates are denatured collagen and collagen peptides. The peptidase has a molecular weight of 124 000 and an isoelectric point at pH 5.1. The pH dependence curve exhibits two maxima, one at pH 7.1 and the other at pH 7.9. The enzymic reaction is completely inhibited by Zn2+ and to a slower degree by Hg2+, Mn2+ and p-hydroxymercuribenzoate. It is not affected by EDTA and KCN but totally blocked by o-phenanthroline. Phenylmethylsulfonylfluoride is completely inhibitory and points to a serine residue in the active site.

Animals↗
PubMed1979

Catecholamine turnover changes in hypothalamus and dorsal midline area of the caudal medulla oblongata of spontaneously hypertensive rats.

The central noradrenaline (NA) and adrenaline (A) turnover in 15--16-week-old stroke prone, spontaneously hypertensive (sp-SH) female rats in an advanced stage of hypertension was found to differ from that of normotensive Wistar-Kyoto (WKy) control rats. The catecholamine (CA) levels were measured after inhibition of dopamine-beta-hydroxylase (DBH) or phenylethanolamine-N-methyltransferase (PNMT). in the hypertensive rats the dopamine (DA) and NA levels and the NA turnover were reduced in the hypothalamus, while in the dorsal part of the caudal medulla oblongata NA levels and A turnover were reduced. Changes in hypothalamic DA and NA mechanisms and in A mechanisms in medulla oblongata may therefore be of importance in the blood pressure regulation of sp-SH rats.

Animals↗
PubMed1979

A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats.

1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.

3-Mercaptopropionic Acid↗
PubMed1979

N-Acetylaminoacyl-p-nitranilidase from human placenta. Purification and some properties.

An enzyme hydrolyzing N-acetylaminoacyl-p-nitroanilides has been isolated from mature human placentae by a six-step procedure comprising extraction from a placenta homogenate, ammonium sulfate fractionation, treatment with isopentyl alcohol, chromatography on CM-Sephadex, protamine sulfate precipitation and gel filtration on an Ultrogel AcA 34 column. About 2500-fold enrichement was achieved from placenta homogenate. The purified enzyme preparation showed a single band on polyacrylamide disc electrophoresis. The molecular weight was estimated to be 380,000 by gel filtration. Placental extracts contain two main isoenzymes of pI 3.9 and 4.5 respectively. Activity was strongly inhibited by chloromercuribenzoate, slightly inhibited by Ca2+ and cysteine; no activation could be detected. The enzyme exhibits an exopeptidase-like activity towards acetyl-dipeptides with a certain specifity towards N-acetylalanyl-alanine; N-acetylalanine-p-nitroanilide, however, is hydrolyzed four times faster. With N-acetylalanine-p-nitroanilide as substrate the pH optimum was 8.0--8.2; Km was 2.13 mmol/l. N-Acetylleucine-p-nitroanilide and N-acetyltyrosine-p-nitroanilide were split slowly; N-acetylalanyl-alanyl-alanine-p-nitroanilide, N-butyloxycarbonyl-alanyl-alanine-p-nitroanilide, unsubstituted analogous aminoacyl-p-nitroanilides and several protein substrates were not hydrolyzed. The functions of the enzyme are still unknown.

Aminopeptidases↗
PubMed1978

[Proteolytic activities in mature human placenta. II. Neutral peptidases and PZ-peptidase (author's transl)].

Continuing our contributions on proteases of human placenta we enriched some unidentified neutral peptidases by chromatographying freeze dried placenta extracts on CM-Sephadex, followed by preparative isoelectric focusing and chromatography on Ultrogel. By this procedure two Acetyl-aminoacyl-p-nitranilidases, three Ala-Ala-p-nitranilidases, one Benzyloxycarbonyl-Ala-Ala-p-nitranilidase, one Carbobenzoxy-Gly-Pro-Arg-p-nitranilidase and one PZ-peptidase could be characterized in greater detail. Here molecular weights, isoelectric points and pH-optima of these enzymes are reported.

Chromatography↗
PubMed1978

Free and conjugated catecholamines in human hypertension.

1. Noradrenaline and adrenaline in the adrenal vein of essential hypertensive patients are almost exclusively (99%) unconjugated or free. However only 17% of dopamine is free, the rest is conjugated. The further the site of sampling from the adrenal vein the closer come the free catecholamines to their normal peripheral venous proportion (noradrenaline + adrenaline 20%, dopamine less than 1% of total catecholamines). Deviations from these patterns help to detect the site and type of secretion of phaeochromocytoma. 2. Essential hypertensive patients have, compared with control subjects, higher conjugated plasma dopamine, less urinary free and conjugated dopamine with blunted urinary free dopamine and sodium responsiveness to frusemide. Conjugated noradrenaline + adrenaline, mean arterial pressure and age are positively interrelated. 3. Patients with primary aldosteronism have elevated plasma and urinary total dopamine. After removal of the adenoma urinary dopamine excretion decreases to normal. 4. Elevated conjugated dopamine appears to reflect a compensatory activation of the dopaminergic vasodilator pathway in hypertension, the total urinary dopamine excretion an intrinsic deficiency or compensatory increase of a dopamine-modulated natriuretic mechanism.

Adrenal Gland Neoplasms↗
PubMed1978

Dopamine-sodium relationship: is dopamine a part of the endogenous natriuretic system?

A possible role of DA as an endogenous natriuretic hormone was reviewed under three aspects: (1) its excretion in response to saline vs. albumin-induced volume expansion, (2) the origin of urinary free DA and (3) urinary free DA excretion in an unexplained salt-retaining condition, idiopathic edema. We have shown (1) that the urinary free DA excretion increase in response to saline is specifically related to salt and does not occur when the same degree of volume expansion is induced by albumin, (2) that this increase in free DA originates in the kidney and (3) that idiopathic edema patients excrete less free DA than control subjects. It is proposed that free DA originating in the kidney is a rather sal than volume-dependent endogenous natriuretic factor. Its deficiency may contribute to excessive sodium retention in idiopathic edema. However, DA is probably not the single natriuretic hormone but a part of a natriuretic system, components of which are other renal vasodilating and natriuretic substances such as prostaglandins and kallikrein-bradykinin.

Animals↗
PubMed1977

[Pz peptidase activity in serum (author's transl)].

Synthetic PZ peptide, synthesized by Wünsch and Heidrich, was used as substrate to determine PZ peptidase activities in the sera of man, rabbit, guinea pig and mouse. The PZ peptidase from rabbit serum was purified 200 fold and characterized. The enzyme has an isoelectric point of 5.0 and pH optima at pH 7.2 and pH 7.9. Its behaviour on gel filtration points to a molecular weight of 60.000 dalton. The peptidase is inhibited by heavy metal ions, SH reagents and serum. Ca ions are EDTA are without any effect. In contrast to collagen peptidases from micro-organisms, the enzyme from rabbit serum does not attack native, but only denatured collagen. The results suggest that PZ peptidases participate in collagen breakdown by cleaving the collagen fragments which are released by the collagenases.

Adult↗
PubMed1977

[Aminoacid-p-nitroanilides splitting activities in the mouse human placenta (author's transl)].

Proteolytic activities of human placental extract are determined with the aid of a sensitive micromethod, based upon the Bratton-Marshall-reaction, and aminoacid-p-nitroanilides as substrates. The activities are differentiated by using 19 substrates, by adding 10 effectors, and by incubating the assays within the pH-range from 6.0--8.4. Besides Oxitocinase- and Aminopeptidase-like activities, a very active neutral peptidase, so far unknown in human placenta, an acid peptidase, e.g. Cathepsin C or Dipeptide-aminopeptidase II, and some other enzymes, not yet indentified by us, are demonstrated.

Amino Acids↗
PubMed1977

[Amino acid-p-nitroanilide-splitting activities in human serum (author's transl)].

Proteolytic, arylamidase-like activities of human serum are determined by using a sensitive micromethod, based upon the Bratton-Marshall-reaction, and amino acid-p-nitroanilides as substrates. Besides the alanine-aminopeptidase and the oxytocinase, the dipeptide-aminopeptidase II, a neutral peptidase, and 6 other peptidases, not yet identified by us, are differentiated with the aid of 19 substrates, by adding 8 effectors, and by incubating the enzyme tests within the pH range 6.0 to 8.4.

Amino Acids↗
PubMed1977

Catecholamine excretion in "idiopathic" edema: decreased dopamine excretion, a pathogenic factor?

In 16 women with idiopathic edema, urinary dopamine excretion was decreased when compared to control women (146 +/- 13 SE ng/ml/m2 vs. 212 +/- 32, P less than 0.05 in the supine position and 140 +/- 9 vs. 199 +/- 20, P less than 0.005 combined values of supine and recumbent positions) and was also lower when pooled values for urinary dopamine excretions both before and after furosemide were compared in idiopathic edema patients and in control subjects (270 +/- 30 ng/ml vs. 480 +/- 70, P less than 0.05). These patients have lower basal sodium excretions, decreased tubular rejection fractions of sodium in the upright position and lower urinary sodium excretions following furosemide administration. The urinary sodium and dopamine excretions before and following furosemide are positively correlated in control (P less than 0.05), idiopathic edema patients (P less than 0.02) and in both groups combined (P less than 0.005). Idiopathic edema patients have normal urinary noradrenaline and adrenaline excretions but, as previously observed, elevated: 1) plasma renin activity while either recumbent or upright, and 2) plasma aldosterone concentrations while upright. These results suggest that a decrease in urinary dopamine, a catecholamine recently recognized to have natriuretic action, possibly reflects a suppression of the renal dopaminergic system and may contribute to the excessive sodium retention in idiopathic edema either directly or indirectly through the renin-aldosterone system.

Adult↗