Angiotensin II Fragment Receptor Binding in the Mouse Brain
Abstract
Angiotensin IV (Ang IV), one of the metabolites of Angiotensin II, is a key player within several systems including the kidneys, brain, and other non-traditional locations. It has functions varying from blood flow regulation, stress response, seizures, learning, and memory acquisition. Administration of Ang IV has been shown to increase cerebral microcirculation, elicit cognitive improvements, improve memory, restore cognitive deficits, and combat memory impairment. In our lab, we developed a new peptide that acts on the angiotensin system, 127I-Ang 1-7. Previous studies showed that 127I-Ang 1-7 is less susceptible to metabolism and ~1000-fold more potent than Ang 1-7 in competing for 125I-Ang 1-7 binding. In addition, 127I-Ang 1-7 also competes for 125I-SI-Ang II binding to the AT1 receptor with moderately high affinity. Thus, the aim of this study was to verify if 127I-Ang 1-7 competes for 125I-Ang IV’s binding site (AT4 receptor) in mouse brains. Competition binding assay showed that 127I-Ang 1-7 competes for 125I-Ang IV binding with a similar IC50 to that for the AT1 receptor. Our data suggests that 127I-Ang 1-7 could be a viable pharmaceutical agent having analogous effects at Ang IV binding sites and potential therapeutic venues include the treatment of cardiovascular and neurodegenerative diseases such as hypertension, Alzheimer’s Disease (AD) or Parkinson’s Disease.
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
Angiotensin II Fragment Receptor Binding in the Mouse Brain
Alvin Shermany Library
Angiotensin IV (Ang IV), one of the metabolites of Angiotensin II, is a key player within several systems including the kidneys, brain, and other non-traditional locations. It has functions varying from blood flow regulation, stress response, seizures, learning, and memory acquisition. Administration of Ang IV has been shown to increase cerebral microcirculation, elicit cognitive improvements, improve memory, restore cognitive deficits, and combat memory impairment. In our lab, we developed a new peptide that acts on the angiotensin system, 127I-Ang 1-7. Previous studies showed that 127I-Ang 1-7 is less susceptible to metabolism and ~1000-fold more potent than Ang 1-7 in competing for 125I-Ang 1-7 binding. In addition, 127I-Ang 1-7 also competes for 125I-SI-Ang II binding to the AT1 receptor with moderately high affinity. Thus, the aim of this study was to verify if 127I-Ang 1-7 competes for 125I-Ang IV’s binding site (AT4 receptor) in mouse brains. Competition binding assay showed that 127I-Ang 1-7 competes for 125I-Ang IV binding with a similar IC50 to that for the AT1 receptor. Our data suggests that 127I-Ang 1-7 could be a viable pharmaceutical agent having analogous effects at Ang IV binding sites and potential therapeutic venues include the treatment of cardiovascular and neurodegenerative diseases such as hypertension, Alzheimer’s Disease (AD) or Parkinson’s Disease.
