A distinct peptidyl dipeptidase that degrades enkephalin: Exceptionally high activity in rabbit kidney

Peptidyl dipeptidase activity distinct from the angiotensin converting enzyme (EC 3.4.15.1) was isolated from membrane fractions of rabbit kidney and lung. The enzyme cleaved Leu-enkephalin at the Gly-Phe bond, releasing Tyr-Gly-Gly and Phe-Leu, and also acted on bradykinin releasing the terminal dipeptide Phe-Arg. In contrast to the converting enzyme, however, this peptidyl dipeptidase did not act on angiotensin I, or on hippuryl His-Leu, nor was it inhibited by captopril (SQ 14225) or by SQ 20881. Kinetic studies indicated a K_m for the kidney enzyme of 80 μM with Leu-enkephalin as a substrate. Our findings indicate that more than one enzyme is present in membrane preparations of lung and kidney inactivating enkephalin, and suggest a role for these enzymes in the peripheral actions of opiate and related peptides.