Degradation of substance P by neurones and glial cells

Neuronal and astroblast-rich cultures from rat brain degrade exogenously added substance P. The rate of degradation is decreased by diisopropylfluorophosphate, phosphoramidon and bacitracin, but not by N-ethylmaleimide or bestatin. When diisopropylfluorophosphate, phosphoramidon and bacitracin are simultaneously present in the culture medium, the degradation of substance P is completely inhibited. These results indicate that the hydrolysis of substance P by intact cells is catalyzed by the post-proline dipeptidylaminopeptidase (EC 3.4.14.5), the thermolysin-like metallopeptidase ("enkephalinase", EC 3.4.24.11) and a yet uncharacterized bacitracin-sensitive activity. While the thermolysin-like metallopeptidase is mainly associated with glial cells, the specific activity of the other enzymes is five times higher in the neuronal culture.