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• W137307620 abstract "The beneficial effects of angiotensin I-converting enzyme (ACE) inhibitors are due in part to augmenting the actions of bradykinin (BK) and Lys-BK on their receptors (R). They inhibit kinin inactivation and thereby stimulate the release of mediators such as prostaglandins, nitric oxide (NO), and others. In addition to inhibiting an enzyme, ACE inhibitors affect BK Rs as allosteric effectors in cultured cells, such as human endothelial cells. ACE inhibitors can potentiate BK and ACE-resistant BK analog’s actions on B2 Rs. They elevate arachidonic acid and NO release as indirect allosteric enhancers acting on a heterodimer formed by human ACE and B2 R. This has been shown by co-immunoprecipitation, immunohistochemistry and fluorescence resonance energy transfer (FRET). After carboxypeptidase N or M removes the C-terminal Arg of kinins, the resulting des-Arg9-BK and des-Arg10-Lys1-BK are inactive on B2 Rs, but are agonists of B1 Rs. Activation of this R leads to prolonged release of NO, synthesized by iNOS. ACE inhibitors are also agonists of the B1 R at a Zn-binding sequence of this heptahelical G protein-coupled R. The site of activation is different from that of the orthosteric peptide ligands; it is on the extracellular loop 2 at residues 195–199. Thus, ACE inhibitors act as direct allosteric agonists. B1 Rs are present mainly in endothelial and other cells after an inflammatory process or induced by cytokines, which also bring about iNOS expression. While constitutively expressed eNOS activation via B2 R results in a short burst of NO, the longer lasting NO release initiated by peptide or ACE inhibitor ligands of the B1R may help to alleviate some detrimental effects in the failing heart." @default.
• W137307620 created "2016-06-24" @default.
• W137307620 creator A5043911586 @default.
• W137307620 creator A5072502183 @default.
• W137307620 creator A5086882346 @default.
• W137307620 date "2009-01-01" @default.
• W137307620 modified "2023-10-10" @default.
• W137307620 title "Kinin Receptors and ACE Inhibitors: An Interrelationship" @default.
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• W137307620 doi "https://doi.org/10.1007/978-1-60761-186-8_11" @default.
• W137307620 hasPublicationYear "2009" @default.
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