In vivo conversion of vasopressin after microinjection into limbic brain areas of rats.

The nonapeptide [Arg8]vasopressin was rapidly degraded with a half-life of lower than 1 minute after local administration into the hippocampus. During the conversion of vasopressin C-terminal fragments were transiently generated. The profile of these metabolites indicated that they were formed by aminopeptidase activity. The aminopeptidase inhibitor amastatin partially inhibited the conversion of vasopressin. A minor pathway involved cleavages in the C-terminus. The results indicate a predominant involvement of aminopeptidase activity in the in vivo metabolism of exogenous vasopressin in the brain. Since products of this metabolic route have been shown to have potent behavioral activities, the behavioral effects seen after microinjection of vasopressin in the brain may be partially due to generation of vasopressin fragments.