Enzymic inactivation of substance P in the central nervous system.
A membrane-bound 'substance P degrading enzyme' (EC 3.4.24.-) from human brain has been purified to apparent homogeneity. The enzyme was extracted from a membrane fraction of human diencephalon with a non-ionic detergent, Brij 35, and activity was monitored by measuring the rate of disappearance of added substance P using radioimmunoassay, bioassay or radiochemical assay. The enzyme is a thermolabile, neutral metallo-endopeptidase with a relative molecular mass of about 50000. It cleaves substance P between Gln6-Phe7, Phe7-Phe8 and Phe8-Gly9, with a ratio of 0.7:1:1. The breakdown products have been identified by a combination of reverse-phase high-performance liquid chromatography and amino acid analysis. A similar cleavage pattern of substance P has also been demonstrated in a synaptic membrane fraction prepared from rat brain, indicating that a 'substance P-degrading enzyme' is the major peptidase responsible for inactivating the peptide in rat brain membranes. The properties of this enzyme distinguished it from previously described peptidases for which substance P is a substrate. Its high selectivity and its affinity for substance P, among many other neuropeptides, suggest that it may be involved in the physiological inactivation of the peptide by neural tissues.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008666:Metalloendopeptidases; D011480:Protease Inhibitors; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000201:enzymology; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D014018:Tissue Distribution
D011480:Protease Inhibitors; D013373:Substance P; D010450:Endopeptidases; D008666:Metalloendopeptidases; C029610:substance P degrading enzyme