Enkephalin-degrading dipeptidyl carboxypeptidase in guinea pig serum: Its properties and action on bioactive peptides

Kase, Ryoichi; Hazato, Tadahiko; Shimamura, Mariko; Kiuchi, Yoshihiro; Katayama, Takashi

doi:10.1016/0003-9861(85)90038-4

Cited by 11 publications

(2 citation statements)

References 21 publications

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“…Thus, captopril has been shown to possess ai-adrenergic inhibitory activity [6,7], to increase the half-life of bradykinin [8], and to inhibit plasma enkcphalinase. a pepti dase capable of degrading enkephalins [9,10], Hence, the relative contribution of each of these to the reduction of blood pressure of cold-treated rats cannot be stated. It therefore seemed worthwhile to undertake another ex periment in which the recently introduced nonpeptide Ang II receptor antagonist, losartan potassium (DuP 753), was administered to rats exposed chronically to cold in order to assess its ability to prevent the development of hypertension under these conditions.…”

Section: Effect Of Chronic Treatment With Losartan Potassium (Dup 753mentioning

confidence: 99%

Effect of Chronic Treatment with Losartan Potassium (DuP 753) on the Elevation of Blood Pressure during Chronic Exposure of Rats to Cold

Fregly¹,

Rossi²,

Bergen³

et al. 1993

Pharmacology

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Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5°C) for 1-3 weeks. The renin-angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II i receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25°C while the remaining three groups were exposed to cold (5°C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed. Chronic exposure to cold increased the weight of heart, kidneys, and brown fat above that of warm-adapted controls. Treatment with losartan failed to prevent the increases in these organ weights. Thus, although treatment with losartan prevented the elevation of systolic blood pressure induced by chronic exposure to cold, it did not prevent cardiac and renal hypertrophy and the increase in brown fat. It would appear that losartan does not affect these and that an elevation of blood pressure does not sustain them.

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Section: Effect Of Chronic Treatment With Losartan Potassium (Dup 753mentioning

confidence: 99%

Effect of Chronic Treatment with Losartan Potassium (DuP 753) on the Elevation of Blood Pressure during Chronic Exposure of Rats to Cold

Fregly¹,

Rossi²,

Bergen³

et al. 1993

Pharmacology

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“…Guinea pig serum ACE degraded enkephalins and their analogs, and the enzyme was inhibited by substance P, angiotensin III, gastrin, and secretin [2].…”

mentioning

confidence: 99%

Species Differences in the Angiotensin Converting Enzyme Activity of Mammalian Serum

Kase

Hazato

Kiuchi

et al. 1986

Experimental Animals

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Identification of Protein Fold Topology Shared between Different Folds Inhibited by Natural Products

McArdle¹,

Quinn²

2007

ChemBioChem

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Natural products have withstood the test of time as therapeutics, but new lead-generation strategies have focussed away from natural products. A new approach that uses natural-product recognition to drive an understanding of biological space might provide an impetus for renewed focus on natural-product starting points. Protein fold topology (PFT) has been shown to be an underlying factor for natural-product recognition. An investigation of natural product inhibitors of the Zincin-like fold has demonstrated their capacity also to inhibit targets of different fold types. Analysis of crystal structure complexes for natural products cocrystallised within different fold types has shown similarity at the PFT level. Two new PFT(T) (where subscript T denotes PFT shared between therapeutic targets) relationships have been established: the Zincin-like- metallohydrolase/oxidoreductase PFT(T) and the Zincin-like-phosphorylase/hydrolase PFT(T). The PFT relationship between a natural product's biosynthetic enzyme and therapeutic target, and now between different fold targets of the same natural product, suggests that PFT is the simplest descriptor of biological space. This fundamental factor for recognition could facilitate a rational approach to drug development guided by natural products.

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Enkephalin-degrading dipeptidyl carboxypeptidase in guinea pig serum: Its properties and action on bioactive peptides

Cited by 11 publications

References 21 publications

Effect of Chronic Treatment with Losartan Potassium (DuP 753) on the Elevation of Blood Pressure during Chronic Exposure of Rats to Cold

Effect of Chronic Treatment with Losartan Potassium (DuP 753) on the Elevation of Blood Pressure during Chronic Exposure of Rats to Cold

Species Differences in the Angiotensin Converting Enzyme Activity of Mammalian Serum

Identification of Protein Fold Topology Shared between Different Folds Inhibited by Natural Products

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