Degradation of substance P by membrane peptidases in the rat substantia nigra: effect of selective inhibitors.
The hydrolysis of substance P by membrane peptidases prepared from the rat substantia nigra was studied in the presence of selective inhibitors. Substance P degradation by synaptic and mitochondrial membranes was completely inhibited by 1,10-phenanthroline (1 mM), a non-specific metallopeptidase inhibitor. Captopril and bestatine, selective inhibitors of angiotensin converting enzyme and aminopeptidases respectively, were without effects. However, phosphoramidon (1 microM), a putative 'enkephalinase' inhibitor, selectively inhibited substance P degradation by synaptic membranes. These results suggest that a phosphoramidon-sensitive endopeptidase may be the principal enzyme responsible for substance P degradation in substantia nigra.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000201:enzymology / Q000378:metabolism*; D013570:Synaptic Membranes / Q000201:enzymology*
D011480:Protease Inhibitors; D013373:Substance P; D010447:Peptide Hydrolases