Captopril and teprotide as discriminators of angiotensin-converting enzyme activity in brain tissue

Abstract

Titrations of angiotensin-converting enzyme (ACE; E.C. 3.4.15.1) present in human serum, as well as in homogenates prepared from post-mortem human caudate or mouse (C57BL1/6J whole brain tissue, were performed with the selective ACE inhibitors, captopril (SQ 14225) and teprotide (SQ 20881). ACE activity present in human serum was more sensitive to inhibition by either inhibitor than the activity present in the brain homogenates. The inhibition curves for the titration of the human serum activity by both inhibitors were sigmoidal while the inhibition curves for the ACE activity present in the brain homogenates were more complex. These results suggest that the brain homogenates contained: (1) at least two species of enzyme activity with properties similar to ACE but with differing affinities for the inhibitors, or (2) substances without ACE activity that are capable of competing with ACE for the binding of the inhibitors. Therefore, measurements of captopril or teprotide-sensitive peptidase activity as well as inhibitor-binding activity may not always reflect ACE concentrations in brain tissue.