Formation of metabolites of [Arg8]vasopressin (AVP) by brain peptidases

Abstract
[Cyt6]AVP-(3–9), an intermediate in the metabolism of AVP-(1–9) in vitro, was used to investigate the mechanism of formation of centrally active AVP metabolites. Exposure of [Cyt6]AVP-(3–9) to rat brain membranes resulted in formation of [Cyt6]AVP-(4–9),-(5–9), [pGlu6,Cyt6]AVP-(4–9) and AVP-(3–5), which were isolated and chemically identified. Products derived from cleavage of the C-terminus of the substrate were absent. Time-course experiments further indicated that the conversion process is predominantly mediby an aminopeptidase-like mechanism. The conversion of [Cyt6]AVP-(3–9) by membranes from hippocampus, amygdala and septum was quantitatively and qualitatively similar. The results point to a major role of aminopeptidase activity in the metabolic conversion of AVP and the formation of centrally active AVP metabolites
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