Characterization of hydrolysis of [leu]enkephalin and D-ala2-[L-leu]enkephalin in rat plasma.

Based on differences in total metabolite accumulation in the presence or absence of selective peptidase inhibitors, rat plasma is found to have its own unique pattern of enkephalin hydrolysis. Approximately 85-90% of the hydrolysis of [leu]enkephalin is attributed to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas "enkephalinase" and aminopeptidase MII activity against [leu]enkephalin are not detectable. Similarly, 80-90% of the hydrolysis of D-ala2-[L-leu] enkephalin (DALLE) is due to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas aminopeptidase MII and enkephalinase activity against this substrate also could not be detected. This is in contrast to the high susceptibility to hydrolysis by enkephalinase, and the low susceptibility to aminopeptidase activity, for DALLE in brain tissue. Among other alternatives, it is suggested that enkephalin hydrolysis in plasma may appear to be unique because of differences in enzyme conformation and/or the availability of a substance(s) that competes with, or alters the binding of, [leu] enkephalin, DALLE or the inhibitors to the enzymes.