Brain peptidase with a unique neuronal localization: The histochemical distribution of dipeptidyl-aminopeptidase II

To assess whether specific peptidases regulate neuropeptide disposition, we have examined histochemically the localization of dipeptidyl-aminopeptidase II (DAP-II). With β-naphthylamide (β-NA) substrates, this enzyme has a selectivity for lysyl-alanyl-β-NA. DAP II staining is highly localized to specific neuronal populations with no staining over glia. Areas in the brain with high densities of DAP II staining include the mitral cells in the olfactory bulb, polymorphic cells in the hippocampus, the paraventricular nucleus of the hypothalamus, and the anterior dorsal thalamus, Purkinje cells, and deep nuclei in the cerebellum. Staining occurs in virtually all cell groups in the inferior colliculus, red nucleus, oculomotor nucleus, and mesencephalic nucleus of the trigeminal nerve, the stratum album of the superior colliculus, as well as most cells in the cochlear and superior olivary nuclei. DAP II localizations do not correlate fully with those on any known neuropeptide. Of the numerous peptides evaluated, only glucagon competes substantially for the DAP II substrate, reducing enzymatic activity by 50% at a 2 x 10^-5 M concentration.