Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro.
[3H]Dynorphin A(1-8) is readily metabolised by rat lumbosacral spinal cord tissue in vitro, affording a variety of products including a significant amount (20% recovered activity) of [3H][Leu5]enkephalin. In the presence of the peptidase inhibitors bestatin, captopril, thiorphan, and leucyl-leucine, [3H][Leu5]enkephalin was the major metabolic product, accounting for 60% of recovered activity. Production of [3H][Leu5]enkephalin was seen across all gross brain regions. The enzyme responsible for the cleavage has an optimal substrate length of 8-13 amino acids and is inhibited by N-[1-(RS)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate, a site-directed inhibitor of the metalloendopeptidase EC 3.4.24.15. However the enzymic breakdown also has properties in common with involvement of endo-oligopeptidase A. Possible consequences of the formation of [Leu5]-enkephalin from the smaller dynorphins are discussed.
Dixon
D M
DM
Department of Chemistry, University of Technology, Loughborough, Leicester, England.
Traynor
J R
JR
D000818:Animals; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism
D004723:Endorphins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D004743:Enkephalin, Leucine; D004399:Dynorphins; C026770:dynorphin (1-8)