Metabolism of neuropeptide Y and calcitonin gene-related peptide by cultivated neurons and glial cells.
Neuropeptide Y and calcitonin gene-related peptide are abundant neuropeptides in the mammalian central and peripheral nervous systems. Their enzymatic degradation by cultivated neurons, astrocytes, and microglia, as well as by purified urokinase-type plasminogen activator, plasmin, thrombin, and trypsin, was investigated in an in vitro approach to elucidate the role of matrix-degrading serine proteinases for inactivation of neuropeptides, especially those of higher amino acid chain length, in the brain. Astrocytes were almost unable to catabolize the peptides. Cultivated neurons and microglia digested neuropeptide Y through cleavage after Arg19, Arg25, Arg33, and Arg35, calcitonin gene-related peptide was cleaved after Arg11 and Arg18. The same cleavage pattern was observed, when neuropeptide Y and calcitonin gene-related peptide were degraded by purified urokinase-type plasminogen activator, plasmin, thrombin, and trypsin. For further characterization of the neuropeptide-degrading serine proteinase activities from cell cultures, urokinase-type plasminogen activator was identified on microglia by immunostaining, whereas tissue-type plasminogen activator mRNA occurred in neurons and astrocytes, but not in microglia. The data are consistent with the possibility that the neuropeptide-degrading serine proteinase activity on neurons and microglia is due to a mixture of plasmin and plasminogen activator activities.
Ludwig
R
R
Anatomisches Institut der Universität Kiel, Germany.
Feindt
J
J
Lucius
R
R
Petersen
A
A
Mentlein
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D006224:Cricetinae; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009457:Neuroglia / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D009478:Neuropeptide Y; D015740:Calcitonin Gene-Related Peptide