Abstract
Abstract. The present study examined whether metabolism of the putative angiotensin-(1-7) receptor agonist and antagonist [angiotensin-(1-7) and D-alanine7angiotensin-(1-7), respectively] altered their ability to interact with angiotensin AT1, AT2, and AT4receptor subtypes. Both angiotensin-(1-7) and D-alanine7angiotensin-(1-7) competed with low affinity for125I-sarcosine1, isoleucine8angiotensin II binding to AT1and AT2receptors in rat liver and adrenal medulla membranes, respectively, and competed with low affinity for125I-angiotensin IV binding to AT4receptors in bovine kidney epithelial cell membranes.In vitrorenal metabolism of the angiotensin-(1-7) receptor ligands (incubating peptides with rat cortical tissue homogenates) had minimal influence on low-affinity binding to AT1and AT2receptors, yet caused a significant and dramatic shift toward high-affinity binding for AT4receptors. Low-affinity angiotensin II binding to the AT4receptor was also shifted toward high-affinity binding following renal metabolism of the peptide. Conversely, angiotensins with high affinity for the AT4receptor (e.g., angiotensin IV) were shifted toward low-affinity binding states following peptide metabolism. Incubation of125I-angiotensin-(1-7) with rat cortical tissue generated the high-affinity AT4receptor ligand125I-angiotensin-(3-7), whereas the renal metabolism of125I-angiotensin II generated both125I-angiotensin-(3-7) and125I-angiotensin IV. These results reveal that renal metabolism of angiotensin-(1-7) receptor ligands and angiotensin II yields products that have high affinity for the AT4receptor and could potentially contribute to the biologic actions of the parent peptide in the kidney.
Publisher
American Society of Nephrology (ASN)
Subject
Nephrology,General Medicine
Cited by
38 articles.
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