title: Angiotensin converting enzyme in human brain discrete localization and biochemical properties.
abstract: Increasing evidence in recent years suggests an important role of the central renin-angiotensin system in cardiovascular regulation. Although angiotensin-converting enzyme (ACE) is a pivotal element in this system, little is known about the enzyme in human brain. Thus, the regional distribution and biochemical properties of ACE were investigated in human brain. The highest activity was found in the hypothalamus (1.23 +/- 0.22 units/mg protein), followed by the caudate nucleus (1.06 +/- 0.23), substantia nigra (0.97 +/- 0.20), medulla oblongata (0.59 +/- 0.17), cerebral cortex (0.30 +/- 0.07), and cerebellum (0.08 +/- 0.02). A high activity was also detected in the pituitary (0.66 +/- 0.12). This enzyme activity was almost completely (70-90%) suppressed by a specific antibody raised against pure human kidney ACE, indicating that the majority of the activity measured is due to true ACE. The molecular weight of the enzyme was 290,000 on gel-exclusion chromatography, 152,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and 158,000 by an immunoprecipitation technique coupled with SDS-PAGE. The optimum pH was 8.0-8.5. The enzyme activity was elevated by increasing concentrations of NaCl, indicating a chloride ion dependency of the enzyme. Most of the enzyme (greater than 80%) was bound to concanavalin A, suggesting the presence of carbohydrate residues. These findings provide evidence for the presence of specific ACE in discrete areas of human brain and suggest that angiotensin II could be generated locally in these structures to exert cardiovascular effects in humans.
authors.affiliation: Third Department of Internal Medicine, Fukushima Medical College, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tani
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D002846:Chromatography, Affinity; D004586:Electrophoresis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D007703:Peptidyl-Dipeptidase A