Formation of metabolites of [Arg8]vasopressin (AVP) by brain peptidases. Conversion of the intermediate [Cyt6]AVP-(3-9).
[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), [pGlu4, 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.
D000626:Aminopeptidases / Q000378:metabolism*; D000679:Amygdala / Q000201:enzymology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D006624:Hippocampus / Q000201:enzymology; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D012688:Septum Pellucidum / Q000201:enzymology
D010446:Peptide Fragments; D001127:Arginine Vasopressin; C048196:argipressin (3-9), (4-1')-disulfide Cys(6)-; D000626:Aminopeptidases