title: Immunocytochemical localization of endopeptidase 24.15 in rat brain.
abstract: Endopeptidase 24.15 (EC 3.4.24.15; EP 24.15), a zinc-metalloendopeptidase highly active in rat testes, brain and pituitary, converts some prodynorphin- and proenkephalin-derived oligopeptides into the corresponding enkephalins and degrades a variety of bioactive peptides including bradykinin, neurotensin, and both angiotensin I and II. The immunocytochemical localization of the enzyme was studied in rat brain using a polyclonal antibody raised in rabbits against a homogeneous preparation of the enzyme isolated from rat testes. The distribution of EP 24.15 immunoreactivity in the brain was widespread, being present in both neurons and glial cells. Surprisingly, however, staining was predominantly nuclear, and not cytoplasmic as expected based on the biochemical demonstration that EP 24.15 activity is predominantly associated with the soluble protein fraction of brain homogenates. Cytoplasmic staining was detected in large neurons but was less intense than the nuclear staining. The highest density of EP 24.15-staining was detected in nuclei of cerebellar Purkinje cells and in hippocampal dentate gyrus cells. High levels of immunoreactivity were also noted in brain areas which contain peptides known to be substrates of the enzyme in vitro. This localization supports a role for EP 24.15 in neuropeptide metabolism, but also suggests an as yet undefined role in nuclear function.
authors.affiliation: Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029.
authors.forename: D P
authors.initials: DP
authors.lastname: Healy
authors.forename: M
authors.initials: M
authors.lastname: Orlowski
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000201:enzymology / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D008666:Metalloendopeptidases / Q000378:metabolism*; D051381:Rats; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D008666:Metalloendopeptidases; C022510:thimet oligopeptidase