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Angiotensin IV displays only low affinity for native insulin‐regulated aminopeptidase (IRAP)
Author(s) -
Demaegdt Heidi,
De Backer JeanPaul,
Lukaszuk Aneta,
Tóth Géza,
Szemenyei Erzsébet,
Tourwé Dirk,
Vauquelin Georges
Publication year - 2012
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2011.00948.x
Subject(s) - aminopeptidase , radioligand , chemistry , enzyme , receptor , angiotensin ii , insulin , angiotensin iii , insulin degrading enzyme , biochemistry , zinc , proteolysis , renin–angiotensin system , biology , endocrinology , angiotensin receptor , amino acid , leucine , organic chemistry , blood pressure
Radioligand binding studies revealed that Ang IV binds to insulin‐regulated aminopeptidase (IRAP)/’AT 4 receptors’ with high affinity. Yet, as these experiments were routinely carried out in the presence of chelators, only the catalytic zinc‐depleted apo‐form of IRAP was labelled. While the chelators remove the catalytic zinc from IRAP and protect Ang IV from proteolytic degradation, the aminopeptidase N selective inhibitor ‘7B’ only exerts the latter effect. By using 7B along with the new stable Ang IV‐analog [ 3 H]AL‐11, we here show that the native enzyme is only a low‐affinity target for Ang IV.