Enkephalin metabolism by microglial aminopeptidase N (CD13).
Rat microglia in culture showed a high capacity to degrade neuropeptides compared with other glial cells. Leu-enkephalin was readily hydrolyzed to free tyrosine and Gly-Gly-Phe-Leu. Inhibition experiments and immunostaining revealed that aminopeptidase N (CD13) on the surface of microglia was responsible for enkephalin cleavage. Endopeptidase-24.11 ("enkephalinase"), angiotensin-converting enzyme, or carboxypeptidases could not be detected on microglia. Aminopeptidase N activity in microglia was considerably higher than in rat peripheral monocytes and macrophages, which both also exhibited low endopeptidase 24.11 activities. Activity of aminopeptidase N was upregulated by culture of microglia on astrocytes and down-regulated by exposure of microglia to lipopolysaccharide. The occurrence of aminopeptidase N on microglia is in line with the view that they originate from the monocytic lineage.
Lucius
R
R
Anatomisches Institut, Universität Kiel, Germany.
Sievers
J
J
Mentlein
R
R
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004745:Enkephalins / Q000378:metabolism*; D007158:Immunologic Techniques; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000201:enzymology*; D009000:Monocytes / Q000378:metabolism; D051381:Rats; D013194:Staining and Labeling
D004745:Enkephalins; D018826:CD13 Antigens