Effect of catecholamines on the activity of rat brain dipeptidyl aminopeptidase

The inhibitory effect of catecholamines, their metabolic intermediates and derivatives on the activity of rat brain dipeptidyl aminopeptidase was studied. The enzyme was extracted from a crude mitochondrial fraction containing lysosomes (and also synaptosomes) and purified by three-step column chromatography. The activity of the purified enzyme was inhibited by a low concentration (IC50 2 approximately 5 mM) of dopamine, norepinephrine and epinephrine. Dihydroxyphenylalanine or dihydroxyphenylacetic acid, each having a carboxyl group, showed only a weak inhibitory effect (IC50 greater than 10 mM). These results suggest the possibility that brain dipeptidyl aminopeptidase activity may be regulated by the changing of the concentration of catecholamines in the central nervous system.