Einosuke Ueda

Peptide Inhibitors of the Renin–Angiotensin System

RENIN is said to split a leucyl–leucine bond in alpha 2 globulin substrate—angiotensinogen—to yield a decapeptide, angiotensin I. Angiotensin I is subsequently converted into an octapeptide, angiotensin II, by a converting enzyme contained in plasma. Angiotensin II has a pressor activity. We have studied the effects of synthetic peptides with a leucyl–leucine bond and their derivatives on the activity of renin in the formation of angiotensin. The peptides were di-, tri-, tetra- and pentapeptides with leucyl–leucine bonds at the C-terminal end, in the middle position, at the N-terminal end or with one of the other structures as shown in Table 1.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

BACKGROUND Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. METHODS ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2 ) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. RESULTS There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. CONCLUSIONS The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

Purification and properties of endopeptidase from rabbit red cells and its process of degradation of angiotensin

Abstract Endopeptidase, showing angiotensinase activity in rabbit red cells, was purified by fractionation with (NH4)2SO4, DEAE-cellulose column chromatography and Sephadex G-200 gel filtration. The specific activity of angiotensinase on the purified preparation was increased about 8000-fold compared with that of the crude hemolysate. The peptide bonds cleaved by the enzyme preparation in [α- l -Asp1, Ile5]-angiotensin II were Arg-Val, Tyr-Ile and Ile-His. It was demonstrated that hydrolysis of the Tyr-Ile bond with the enzyme was the first step in the inactivation process of angiotensin. The results indicated that the purified so-called angiotensinase might be an endopeptidase without hydrolytic activity on casein, p- toluenesulfonyl - l - arginine methyl ester and acetyl- l -tyrosine ethyl ester.

Angiotensinase in red cells.

Abstract Comparison of angiotensinase activity in red cells and plasma from rabbits and the fractionation of the enzyme were studied. 1. (1) Angiotensinase activity in red cells from humans and rabbits was much higher than that in plasma. Angiotensinase activity in red cells and plasma, when horizontal starch block electrophoresis was employed, was the highest in the albumin position under the conditions employed. In red cells, two additional fractions showing angiotensinase activity were demonstrated in the position toward the anodal side further than the albumin position. 2. (2) In order to isolate the enzyme in the albumin position in red cells from rabbit, fractionation with ammonium sulfate and DEAE Sephadex A-50 column chromatography were made. Specific activity of angiotensinase in the purified preparation was increased about 300-fold or more compared with that of the crude hemolysate. It was shown that the activity of angiotensinase was not due to leucine aminopeptidase.

Inhibition of angiotensin I converting enzyme and kininase in rabbit plasma by bradykinin potentiating peptide B (Pyr-Gly-Leu-Pro-Arg-Pro-Lys-Ile-Pro-Pro).

Das Bradykinin-potenzierende Peptid B (Pyr-Gly-Leu-Pro-Pro-Arg-Pro-Lys-Ile-Pro-Pro) verhindert in vitro und in vivo die Aktivität der Plasmakininase und des «converting»-Enzyms.

Inhibitory effect of bile acids on renin angiotensinogen reaction system

Die Wirkung verschiedener synthetischer Derivate der Gallensäure wurden auf die Reninaktivität in Form des Angiotensin in vitro untersucht und es wird darauf hingewiesen, dass die 7-Desoxyform der Gallensäuren für die Renininhibition wesentlich ist.

Antihypertensive effect of purified enzyme showing angiotensinase activity from rabbit red cells in rats

In der akuten Phase der Goldblatt-Hypertonie der Ratte verhinderte die Injektion von reiner Angiotensinase ein Aussteigen des Blutdruckes. Die Behandlung war unwirksam bei chronischem Hochdruck.

Plasma angiotensinase activity in liver disease

Abstract The electrophoretic detection of the appearance of plasma angiotensinase activity in the γ-globulin zone, named angiotensinase G, in patients with liver damage was studied using rabbits. Angiotensinase G could not be detected either in liver extract from normal rabbits or from rabbits with experimental liver damage. When normal rabbit plasma was incubated together with liver extract, angiotensinase G activity was demonstrated electrophoretically in the incubation mixture. In vitro experiments indicated that γ- or β- globulin fractions of plasma and a heat unstable substance in microsome fractions of liver cells were essential for the formation of angiotensinase G.

A New Depressor Principle in Liver from Normal Rabbit

The depressor principle, located only in micro-some fraction of normal rabbit liver cell by the method of SCHNEIDER, was isolated by heat treatment, fractionation of ammonium sulfate between 0-70% saturation of the supernatant, DEAE-Sephadex A-50 column chromatography and zone electrophoresis. Intravenous injection of the principle showed relatively a long sustained depressor effect in comparison with that of bradykinin or adenosine in a normal rabbit and rat. The ultraviolet absorption maximum of the principle was 256mμ. The mean molecular weight was 36, 000 by ARCHIBALD method and about 90% was RNA. Nucleotide analysis showed CMP 20%, UMP 14%, AMP 7% and GMP 59%.