Inhibition of the Renin-Angiotensinogen Reaction by Pepstatin

Gross, F.; Lazar, Jeffrey D.; Orth, H.

doi:10.1126/science.175.4022.656

Cited by 125 publications

(30 citation statements)

References 5 publications

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“…2). The value of K i was more than 60 times higher than that of K m and was much higher than that of other potent renin inhibitors (32,33). The K m was in the similar range as reported previously (24).…”

Section: Discussionsupporting

confidence: 68%

A dipeptide YY derived from royal jelly proteins inhibits renin activity

Sultana

Nabi²,

Nasir³

et al. 2008

Int J Mol Med

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Abstract. Renin is the rate limiting enzyme in the reninangiotensin (RA) system that regulates blood pressure and electrolyte balance. In this study, we investigated the renin inhibitory effect of a royal jelly (RJ)-derived peptide. A dipeptide YY was isolated from the digested fraction of RJ proteins by proteases and was found to inhibit human renin activity. The inhibition constant (K i ) of YY was estimated to be 10 μM when the K m was 0.16 μM using sheep angiotensinogen as the substrate. The peptide was observed to lower blood pressure in spontaneously hypertensive rats.

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Section: Discussionsupporting

confidence: 68%

A dipeptide YY derived from royal jelly proteins inhibits renin activity

Sultana

Nabi²,

Nasir³

et al. 2008

Int J Mol Med

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“…To determine whether cellular Al generation was dependent on the activity of intracellular aspartyl proteases, we evaluated the effect of pepstatin, the specific inhibitor for these enzymes (Gross et al, 1972). Cellular sonicates were incubated at 37°C with 0.1-1 DIM pepstatin at pH 5.5 for 1 hour.…”

Section: Characterization and Identification Of Cellular Renin-like Amentioning

confidence: 99%

Renin expression by vascular endothelial cells in culture.

Lilly¹,

Pratt²,

Alexander³

et al. 1985

Circulation Research

111

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SUMMARY. Cultured bovine aortic endothelial cells were examined for renin activity by biochemical, immunological, and immunohistochemical techniques. When cell sonicates were incubated with renin substrate, linear generation of angiotensin I was observed (1.12 ± 0.2 ng angiotensin I/10 6 cells per hr). The effect of pH on this activity was similar to that of bovine renal renin, and renin antibodies inhibited a large portion of the enzymatic activity. Furthermore, immunofluorescence microscopy with antirenin antisera confirmed the presence of renin within these cells. Biosynthetic radiolabeling, followed by immunoprecipitation, demonstrated de novo synthesis of a renin precursor in the endothelial cells, which was processed to a more mature protein. Thus, bovine aortic endothelial cells in culture contain and biosynthesize renin, a key component of the renin-angiotensin system. The expression of renin activity by endothelium may contribute to the local regulation of vascular tone. (Ore Res 57: 312-318, 1985)

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“…Proof of principle was established first by use of immunization against renin, 14 followed by studies with a nonspecific inhibitor, pepstatin, and finally with peptide mimics of either prorenin or of the renin substrate angiotensinogen. 15,16 Several of the peptide mimics were developed as possible drugs, and the invaluable knowledge gained has already been well described in the review of renin inhibitors by Staessen et al 17 Parenteral administration of peptide inhibitors to salt-depleted subjects confirmed proof of principle as an effective mechanism of blood pressure reduction, 18 and the development of tetrapeptides led to clinical investigation of orally administered compounds (enalkiren, remikiren, zankiren). 19 However, these compounds had predictably low bioavailability of Ͻ2% and short half-lives.…”

Section: The Target For Direct Renin Inhibitionmentioning

confidence: 99%

Aliskiren

Brown

2008

Circulation

119

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Abstract-Aliskiren is the first orally active inhibitor of renin to be approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg, there are dose-related falls in blood pressure comparable to those seen with other major classes of antihypertensive drugs and that these falls are associated with a placebo level of side effects. Aliskiren was found to be effective either as monotherapy or in combination with drugs from the other major classes. As expected, there was a greater benefit from adding aliskiren to natriuretic drugs than to other blockers of the renin system. However, there was also some consistent benefit from dual renin blockade. Aliskiren is likely to be of most value in patients uncontrolled by, or intolerant of, other classes. Rational understanding of the renin system will maximize its value, for instance, by encouraging greater use of natriuretic agents in patients with resistant hypertension to render their hypertension renin dependent. Whether there are cardiovascular benefits other than blood pressure control in blocking the renin system remains to be demonstrated. It is hoped that long-term outcome studies with aliskiren will finally allow this question to be answered. (Circulation. 2008;118:773-784.)

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Inhibition of the Renin-Angiotensinogen Reaction by Pepstatin

Abstract: Pepstatin, an N-acylated pentapeptide obtained from culture filtrates of actinomycetes and first characterized as an inhibitor of pepsin, produces inhibition of the renin-substrate reaction both in vitro and in vivo.

Cited by 125 publications

References 5 publications

A dipeptide YY derived from royal jelly proteins inhibits renin activity

A dipeptide YY derived from royal jelly proteins inhibits renin activity

Renin expression by vascular endothelial cells in culture.

Aliskiren

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