Cleavage of Peptide Bonds by Angiotensin I Converting Enzyme

Ra, Skidgel; Eg, Erdös

doi:10.1007/978-3-0348-9299-5_30

Cited by 15 publications

(11 citation statements)

References 11 publications

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“…Other proteases also degrade SP in the extracellular fluid. Angiotensin-converting enzyme (ACE, EC 3.4.15.1) degrades SP (22), and administration of ACE inhibitors induces widespread plasma extravasation that is prevented by an NK1R antagonist (23). The elevated plasma extravasation observed in mice lacking NEP or treated with inhibitors of NEP and ACE may be mediated by diminished degradation of other peptides in addition to SP.…”

Section: Nep Terminates the Proinf Lammatory Effects Of Spmentioning

confidence: 99%

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Sturiale

Barbara

Qiu

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

162

112

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Neurogenic inf lammation is regulated by sensory nerves and characterized by extravasation of plasma proteins and infiltration of neutrophils from post-capillary venules and arteriolar vasodilatation. Although it is well established that substance P (SP) interacts with the neurokinin 1 receptor (NK1R) to initiate neurogenic inf lammation, the mechanisms that terminate inf lammation are unknown. We examined whether neutral endopeptidase (NEP), a cellsurface enzyme that degrades SP in the extracellular f luid, terminates neurogenic inf lammation in the colon. In NEP knockout mice, the SP concentration in the colon was Ϸ2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP. The extravasation of Evans blue-labeled plasma proteins in the colon of knockout mice under basal conditions was Ϸ4-fold higher than in wild-type mice. This elevated plasma leak was attenuated by recombinant NEP or the NK1R antagonist SR140333, and is thus caused by diminished degradation of SP. To determine whether deletion of NEP predisposes mice to uncontrolled inf lammation, we compared dinitrobenzene sulfonic acid-induced colitis in wild-type and knockout mice. The severity of colitis, determined by macroscopic and histologic scoring and by myeloperoxidase activity, was markedly worse in knockout than wild-type mice after 3 and 7 days. The exacerbated inf lammation in knockout mice was prevented by recombinant NEP and SR140333. Thus, NEP maintains low levels of SP in the extracellular f luid under basal conditions and terminates its proinf lammatory effects. Because we have previously shown that intestinal inf lammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inf lammation.

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Section: Nep Terminates the Proinf Lammatory Effects Of Spmentioning

confidence: 99%

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Sturiale

Barbara

Qiu

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

162

112

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“…Medications and drugs to avoid in patients with HAE 28 a. Angiotensin-converting enzyme inhibitors. [29][30][31] b. Estrogen contraceptives. 6,13,[32][33][34][35][36][37][38] c. Plasminogen activators are a theoretic risk, but the benefit might outweigh the risk.…”

Section: Vaccination Recommendationsmentioning

confidence: 99%

Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema

Bowen

Cicardi

Farkas

et al. 2004

Journal of Allergy and Clinical Immunology

186

190

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C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Société d'Angioédème Héréditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future.

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“…ACE is a bivalent dipeptidyl carboxyl metallopeptidase present in soluble form in bodily fluids and as a membrane bound form on endothelial, epithelial or neuroepithelial cells of several organs including the heart. ACE regulates the balance between the KKS and RAS by cleaving the C-terminal dipeptide Phe-Arg from bradykinin, leading to its inactivation, and by binding to angiotensin I (AngI) to cleave its C-terminal dipeptide, His-Leu, creating angiotensin II (AngII), respectively [10].…”

Section: The Kallikrein-kinin System and The Renin-angiotensin Systemmentioning

confidence: 99%

Treatment of Experimental Myocarditis via Modulation of the Renin-Angiotensin System

Daniels¹,

Hyland²,

Engman³

2007

CPD

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The renin-angiotensin system is primarily responsible for regulating vascular tone. Drugs that inhibit this pathway, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, are widely used to treat hypertension and a variety of cardiomyopathies. Recent studies have shown that, in addition to reducing blood pressure, these drugs also modulate inflammation, adhesion molecule expression, and fibrosis. To assess the therapeutic potential of these inhibitory agents for the treatment of inflammatory heart disease, the drugs have been tested in experimental models of infectious and autoimmune myocarditis. This review summarizes the results of studies examining the efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor antagonists for the treatment of mouse models of virus-induced and parasite-induced myocarditis, as well as autoimmune cardiomyopathy. The collective results strongly support the use of renin-angiotensin modulation for the treatment of myocarditis. Importantly, this therapeutic approach seems to downregulate autoimmunity without causing immune suppression which may enhance the survival of the disease-initiating infectious agent.

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Cleavage of Peptide Bonds by Angiotensin I Converting Enzyme

Cited by 15 publications

References 11 publications

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema

Treatment of Experimental Myocarditis via Modulation of the Renin-Angiotensin System

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