Metabolic Inactivation of Angiotensin 1-7 (Ang 1-7)
Abstract
The renin-angiotensin system (RAS) plays a role in the control of the cardiovascular system by modulating blood pressure. While Angiotensin II (Ang II) serves as a vasoconstrictor and is the most well-known of the RAS peptides, Angiotensin 1-7 (Ang 1-7) is a peptide gaining interest in its countereffects to Ang II and may serve as its antagonist. However, the rapid metabolism and subsequent inactivation of Ang 1-7 precludes its use in radioactive binding assays. For this reason, peptidase inhibitors were added to assays involving 125I-Ang1-7 or an analog 125I-alamandine. This study uses high pressure liquid chromatography (HPLC) to determine the metabolism of Ang1-7 under conditions of the receptor binding assay. To protect the Ang1-7 from metabolic enzymes, enzyme inhibitors were added. While these inhibitors partially protected Ang1-7 from metabolic inactivation, they also prevented 125IAng1-7 from binding to its receptor, which precludes doing proper receptor binding assays. Therefore, this experiment studied the interaction of 125IAng1-7 with its binding sites, which may be enzymes rather than receptors. A further objective is to determine the metabolism of non-radioactive 127I-Ang1-7 and the possibility that 127I-Ang 1-7 could protect Ang1-7 from metabolic inactivation. These studies will provide insight on the receptor for Ang1-7 and the binding site for radioactive, 125I-Ang1-7. Potential therapeutic significance resulting from these studies could be the ability of non-radioactive 127I-Ang1-7 to protect Ang1-7 from metabolic degradation.
Faculty Sponsors
Dr. Robert Speth, Dr. Filipe Stoyell-Conti
Project Type
Event
Location
Alvin Shermany Library
Start Date
4-5-2019 1:00 PM
End Date
4-5-2019 5:00 PM
Metabolic Inactivation of Angiotensin 1-7 (Ang 1-7)
Alvin Shermany Library
The renin-angiotensin system (RAS) plays a role in the control of the cardiovascular system by modulating blood pressure. While Angiotensin II (Ang II) serves as a vasoconstrictor and is the most well-known of the RAS peptides, Angiotensin 1-7 (Ang 1-7) is a peptide gaining interest in its countereffects to Ang II and may serve as its antagonist. However, the rapid metabolism and subsequent inactivation of Ang 1-7 precludes its use in radioactive binding assays. For this reason, peptidase inhibitors were added to assays involving 125I-Ang1-7 or an analog 125I-alamandine. This study uses high pressure liquid chromatography (HPLC) to determine the metabolism of Ang1-7 under conditions of the receptor binding assay. To protect the Ang1-7 from metabolic enzymes, enzyme inhibitors were added. While these inhibitors partially protected Ang1-7 from metabolic inactivation, they also prevented 125IAng1-7 from binding to its receptor, which precludes doing proper receptor binding assays. Therefore, this experiment studied the interaction of 125IAng1-7 with its binding sites, which may be enzymes rather than receptors. A further objective is to determine the metabolism of non-radioactive 127I-Ang1-7 and the possibility that 127I-Ang 1-7 could protect Ang1-7 from metabolic inactivation. These studies will provide insight on the receptor for Ang1-7 and the binding site for radioactive, 125I-Ang1-7. Potential therapeutic significance resulting from these studies could be the ability of non-radioactive 127I-Ang1-7 to protect Ang1-7 from metabolic degradation.
