Metalloendopeptidase (EC 3.4.24.11) but not angiotensin converting enzyme is involved in the inactivation of substance P by synaptic membranes of the rat substantia nigra.
Substance P is a neuropeptide released in vivo from the substantia nigra, the principal substance P nerve terminal region in the rat brain. Its inactivation was investigated in a purified nigral synaptic membrane preparation. The membrane-bound enzyme shares many features with the endopeptidase 24-11 (EC 3.4.24.11): 1) hydrolysis of peptide bonds Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10, 2) sensitivity to the inhibition by phosphoramidon and 3) relative affinity for substance P. Bestatine and captopril inhibit only the hydrolysis of the metabolites. These results suggest that substance P is inactivated in substantia nigra by endopeptidase 24-11 and that a bestatin-sensitive aminopeptidase and angiotensin converting enzyme may play a role in subsequent degradation of the substance P metabolites.
Oblin
A
A
Laboratoires d'Etudes et de Recherches Synthélabo (L.E.R.S.), Bagneux, France.
Danse
M J
MJ
Zivkovic
B
B
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004789:Enzyme Activation; D006020:Glycopeptides / Q000494:pharmacology; D006868:Hydrolysis; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000201:enzymology*; D013379:Substrate Specificity; D013570:Synaptic Membranes / Q000201:enzymology*
D006020:Glycopeptides; D013373:Substance P; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon