• Bulletin of the Korean Chemical Society
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• 제17권2호
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• pp.182-188
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• 1996

Early attempts to identify plausible conformations of a linear octapeptide hormone, angiotensin-II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), using various theoretical and experimental methods, have led to various conformational models. So far, no consensus has been made about the solution phase structure and the receptor binding structure of angiotensin-II. The ultimate goal for the conformation study of the peptide hormone is to develop a new potent drug. Therefore, we have devised a strategy for designing the pharmacophore by studying thermodynamically possible conformations of various kinds of angiotensin-II antagonists and angiotensin-II.

• BMB Reports
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• 제29권1호
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• pp.11-16
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• 1996

The present study showed that receptor-mediated activation of rabbit kidney proximal tubule cells by angiotensin II, the $Ca^{2+}$ ionophore A23187, or the protein kinase C activator phorbol myristate acetate (PMA) all stimulated phospholipase D (PLD). This was demonstrated by the increased formation of phosphatidic acid, and in the presence of 0.5% ethanol, phosphatidylethanol (PEt) accumulation. Angiotensin II leads to a rapid increase in phosphatidic acid and diacylglycerol, and phosphatidic acid formation preceeded the formation of diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine hydrolyzed by Pill. On the other hand, EGTA substantially attenuated angiotensin II and A23187-induced PEt formation, and when the cells were pretreated with verapamil angiotensin II-induced Pill activation was completely abolished. These results provide the evidence that calcium ion influx is essential for the agonist-induced Pill activation. In addition, staurosporine, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but was ineffective on angiotensin II-induced PEt accumulation. $GTP{\gamma}S$ also stimulates PEt formation in digitonin-permeabilized cells, but pretreatment of the cells with pertussis toxin failed to suppress angiotensin II-induced PEt formation. From these results, we conclude that in the rabbit kidney proximal tubule cells the mechanisms of angiotensin II- and PMA-induced Pill activation are different from each other and mediated via a pertussis toxin-insensitive trimeric G protein.

• Tuberculosis and Respiratory Diseases
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• 제52권5호
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• pp.506-518
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• 2002

연구배경 : 특발성 간질성 폐렴에서 폐섬유화를 일으키는 주된 세포인 섬유아세포를 활성화시키면서 폐포 상피 세포의 세포사멸에 큰 역할을 하는 것으로 알려진 angiotensin II와 antiotensin converting enzyrne(ACE) 혈청 수치를 측정하여, 이들과 환자의 폐기능, 호흡곤란 정도, 기관지폐포세척액에서 세포 분획과의 관계를 알아보고자 하였다. 방 법 : 저자들은 가천의대 길병원에서 특발성 간질성 폐렴으로 진단된 23명의 환자를 대상으로 하였다. 이들 모두에서 내원 당시 혈청 ACE와 angiotensin II를 측정하여 각각을 증가군과 비증가군으로 나누었으며 환자들의 폐기능 검사, 호흡곤란 정도 지수, 기관지폐포세척술상 세포 분획을 측정하여 비교하였다. 결 과 : 전체 환자 23명에서 혈청 ACE 증가군은 14명, 비증가군은 9명이었고, angiotensin II의 경우 증가군이 14명, 비증가군이 9명이였다. DLCO%의 경우 angiotensin II 비증가군이 $64.0{\pm}19.8%$, 증가군이 $51.6{\pm}18.7%$로 증가군에서 유의한 수준으로 감소된 소견을 보였다(p=0.021). 결 론 : 특발성 간질성 폐렴 환자 중 혈청 angiotensin II의 비정상적인 증가가 있는 군에서 폐확산능의 유의한 감소가 보여 angiotensin II의 증가가 폐 섬유화의 진행 과정에서 중요한 역할을 할 것으로 생각되며, 그 기전에 대한 연구가 지속적으로 필요할 것으로 사료된다.

• The Korean Journal of Physiology
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• 제23권2호
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• pp.363-375
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• 1989

It has been well known that peripheral infusion of angiotensin II results in an increase of blood pressure, and an elevation of aldosterone secretion, and an inhibition of renin relase. However, the direct effect of angiotensin II on renal function has not been clearly established. In the present study, to investigate the effect of angiotensin II on renal function and renin release, angiotensin II (0.3, 3 and 10 ng/kg/min) was infused into a unilateral renal artery of the unanesthetized rabbit and changes in renal function and active and inactive renin secretion rate (ARSR, IRSR) were measured. In addition, to determine the relationship between the renal effect of angiotensin II and adenosine, the angiotensin II effect was evaluated in the presence of simultaneously infused 8-phenyltheophylline (8-PT, 30 nmole/min), adenosine A 1 receptor antagonist. Angiotensin II infusion at dose less than 10 ng/kg/min decreased urine flow, clearances of para-amino-hippuric acid and creatinine, and urinary excretion of electrolytes in dose-dependent manner. The changes in urine flow and sodium excretion were significantly correlated with the change in renal hemodynamics. Infusion of angiotensin II at 10 ng/kg/min also decreased ARSR, but it has no significant effect on IRSR. The change in ARSR was inversely correlated with the change in IRSR. The plasma concentration of catecholamine was not altered by an intarenal infusion of angiotensin II. In the presence of 8-PT in the infusate, the effect of angiotensin II on renal function was significantly attenuated, but that on renin secretion was not modified. These results suggest that the reduction in urine flow and Na excretion during intrarenal infusion of angiotensin II was not due to direct inhibitions of renal tubular transport systems, but to alterations of renal hemodynamics which may partly be mediated by the adenosine receptor.

• Archives of Pharmacal Research
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• 제14권3호
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• pp.231-236
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• 1991

The high affinity binding sites for angiotensin II were solubilized from rat liver membranes by treatment with CHAPS. The binding protein was also partially purified by angiotensin III inhibitor-coupled Affi-gel affinity chromatography. Binding to the intact membrances as well as to the solubilized preparation was specific and saturable. According to the Scatchard plot, the membrane preparations exhibited a single class of high affinity binding sites with a Kd OF 0.71 nM. The solubilized preparation also showed the presence of a single class of bindings sites with less affinity (Kd of 14 nM). Meanwhile the competition studies using angiotensin II analogues represented two separate binding sites for angiotensin II and single binding site for antagonist. These latter findings were correlated to the results provided by Garrison's research group. More works are needed to clarify this discrepancy.

• 약학회지
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• 제33권6호
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• pp.345-349
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• 1989

This paper was attempted to investigate effect of angiotensin inhibitor (loading dose 25, 50, $100{\mu}g/kg$ and maintenance dose 12.5, 25, $50{\mu}g/kg/hr$) on the pharmacokinetics of furosemide (5 mg/kg i.v) in rabbit. The plasma concentrations of furosemide increased by angiotensin inhibitor and the relative bioavailability of furosemide increased from 118.1% to 193.2% by the inhibitor. The protein binding of furosemide decreased by angiotensin inhibitor in bovine serum albumin ($2.17\;{\times}\;10^{-4}M$) by equilibrium dialysis method. Consequently, dosage regimen of furosemide might be adjusted carefully when furosemide is administered with angiotensin inhibitor.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.319-328
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• 2020

High fructose intake induces hyperglycemia and hypertension. However, the mechanism by which fructose induces metabolic syndrome is largely unknown. We hypothesized that high fructose intake induces activation of the renin-angiotensin system (RAS), resulting in hypertension and metabolic syndrome. We provided 11-week-old Sprague-Dawley rats with drinking water, with or without 20% fructose, for two weeks. We measured serum renin, angiotensin II (Ang II), and aldosterone (Aldo) using ELISA kits. The expression of RAS genes was determined by quantitative reverse transcription polymerase chain reaction. High fructose intake increased body weight and water retention, regardless of food intake or urine volume. After two weeks, fructose intake induced glucose intolerance and hypertension. High fructose intake increased serum renin, Ang II, triglyceride, and cholesterol levels, but not Aldo levels. High fructose intake increased the expression of angiotensinogen in the liver; angiotensin-converting enzyme in the lungs; and renin, angiotensin II type 1a receptor (AT1aR), and angiotensin II type 1b receptor (AT1bR) in the kidneys. However, expression of AT1aR and AT1bR in the adrenal glands did not increase in rats given fructose. Taken together, these results indicate that high fructose intake induces activation of RAS, resulting in hypertension and metabolic syndrome.

• 약학회지
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• 제33권3호
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• pp.183-190
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• 1989

Angiotensin II, adminstered (infused or injected) intravenously, elicited the antidiuretic action with the decreased parameters of renal function at a small dose ($0.01\;{\mu}g/kg/min$), whereas, at a large dose (0.03, $0.1\;{\mu}g/kg/min$ and $5.0\;{\mu}g/kg$), it produced the diuretic action accompanied the increased amounts of sodium and potassium excreted in urine ($E_{Na}\;and\;R_K$). At this time, glomerular filtration rates (GFR) were weakened slightly and renal plasma flows (RPF) were reduced markedly, and then filtration fractions (FF) were increased. Angiotensin II, infused into a renal artery, exhibited antidiuretic action at a small dose ($0.003\;{\mu}g/kg/min$), and diuretic action at a large dose ($0.01\;{\mu}g/kg/min$), only in infused (experimental) kidney. The mechanism of the action was similar to the cases of the intravenous angiotensin II. The above results suggest that angiotensin II of a large dose produced diuretic action due to mechanism inhibiting reabsorption of electrolytes in renal tubules, mainly in proximal tubule in dog.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.343-347
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• 2006

The present study was designed to investigate the effects renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and local natriuretic peptide (NP) system for glomerulopathy induced in the experimental bilateral ureteral obstructive rats. Sprague-Dawley male rats ($200{\sim}220g$ body weight) were bilaterally obstructed by ligation of the proximal ureters for 24 hours. Control rats were treated in the same ways, except that no ligature was made. The glomeruli were isolated from cortex by graded sieve methods, and the mRNA expressions of local renin-angiotensin system (RAS), aldosterone synthase (CYP11B2), endothelin-1 (ET-1) and NP system were determined by real-time polymerase chain reaction. Following the bilateral ureteral obstruction, the mRNA expressions of renin, angiotensin converting enzyme 1 as well as ET-1 were increased, while that of angiotensin converting enzyme 2 was not changed. The expressions of CYP11B2 and angiotensin II receptors were not changed. C-type natriuretic peptide (CNP) expression was increased, while its receptors (natriuretic peptide receptor-B) were not changed. We suggest that the upregulation of local RAS and ET playa role in the progressive glomerular injury, and that the enhanced CNP activity also plays a compensatory role in obstructive uropathy in the glomerulus.

• Molecules and Cells
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• 제28권1호
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• pp.25-30
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• 2009

${\beta}$-Arrestins turn off G protein-mediated signals and initiate distinct G protein-independent signaling pathways. We previously demonstrated that angiotensin $AT_1$ receptorbound ${\beta}$-arrestin 1 is cleaved after $Phe^{388}$ upon angiotensin II stimulation. The mechanism and signaling pathway of angiotensin II-induced ${\beta}$-arrestin cleavage remain largely unknown. Here, we show that protein Tyr phosphatase activity is involved in the regulation of ${\beta}$-arrestin 1 cleavage. Tagging of green fluorescent protein (GFP) either to the N-terminus or C-terminus of ${\beta}$-arrestin 1 induced conformational changes and the cleavage of ${\beta}$-arrestin 1 without angiotensin $AT_1$ receptor activation. Orthovanadate and molybdate, inhibitors of protein Tyr phosphatase, attenuated the cleavage of C-terminal GFP-tagged ${\beta}$-arrestin 1 in vitro. The inhibitory effects of okadaic acid and pyrophosphate, which are inhibitors of protein Ser/Thr phosphatase, were less than those of protein Tyr phosphatase inhibitors. Cell-permeable pervanadate inhibited angiotensin II-induced cleavage of ${\beta}$-arrestin 1 in COS-1 cells. Our findings suggest that Tyr phosphorylation signaling is involved in the regulation of angiotensin II-induced ${\beta}$-arrestin cleavage.