FORMATION OF [LEU5]ENKEPHALIN FROM DYNORPHIN-A(1-8) BY RAT CENTRAL NERVOUS-TISSUE INVITRO

被引:26
作者
DIXON, DM [1 ]
TRAYNOR, JR [1 ]
机构
[1] LOUGHBOROUGH UNIV TECHNOL,DEPT CHEM,LOUGHBOROUGH LE11 3TU,LEICS,ENGLAND
关键词
Dynorphin A(1–8); Endopeptidase; Metabolism; Peptidase inhibitors; Rat brain and spinal cord; Leu[!sup]5[!/sup]]Enkephalin;
D O I
10.1111/j.1471-4159.1990.tb01972.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
[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 leucylleucine, [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 b 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. Copyright © 1990, Wiley Blackwell. All rights reserved
引用
收藏
页码:1379 / 1385
页数:7
相关论文
共 28 条
[1]   SYNAPTOSOMAL MEMBRANE-BOUND FORM OF ENDOPEPTIDASE-24.15 GENERATES LEU-ENKEPHALIN FROM DYNORPHIN1-8, ALPHA-NEUENDORPHIN-BETA-NEOENDORPHIN, AND MET-ENKEPHALIN FROM MET-ENKEPHALIN-ARG6-GLY7-LEU8 [J].
ACKER, GR ;
MOLINEAUX, C ;
ORLOWSKI, M .
JOURNAL OF NEUROCHEMISTRY, 1987, 48 (01) :284-292
[2]  
ALBERT A, 1979, SELECTIVE TOXICITY, P385
[3]   PREPARATION, ASSAY, AND PARTIAL CHARACTERIZATION OF A NEUTRAL ENDOPEPTIDASE FROM RABBIT BRAIN [J].
CAMARGO, ACM ;
SHAPANKA, R ;
GREENE, LJ .
BIOCHEMISTRY, 1973, 12 (09) :1838-1844
[4]   BRAIN ENDO-OLIGOPEPTIDASE-A, A PUTATIVE ENKEPHALIN CONVERTING ENZYME [J].
CAMARGO, ACM ;
OLIVEIRA, EB ;
TOFFOLETTO, O ;
METTERS, KM ;
ROSSIER, J .
JOURNAL OF NEUROCHEMISTRY, 1987, 48 (04) :1258-1263
[5]   ACTIVE-SITE DIRECTED N-CARBOXYMETHYL PEPTIDE INHIBITORS OF A SOLUBLE METALLOENDOPEPTIDASE FROM RAT-BRAIN [J].
CHU, TG ;
ORLOWSKI, M .
BIOCHEMISTRY, 1984, 23 (16) :3598-3603
[6]  
CHU TG, 1985, ENDOCRINOLOGY, V116, P1416
[7]   DYNORPHIN1-8 AND DYNORPHIN1-9 ARE LIGANDS FOR THE KAPPA-SUBTYPE OF OPIATE RECEPTOR [J].
CORBETT, AD ;
PATERSON, SJ ;
MCKNIGHT, AT ;
MAGNAN, J ;
KOSTERLITZ, HW .
NATURE, 1982, 299 (5878) :79-81
[8]  
DIXON D, 1987, British Journal of Pharmacology, V91, p300P
[9]   ISOLATION AND AMINO-ACID SEQUENCE-ANALYSIS OF A 4,000-DALTON DYNORPHIN FROM PORCINE PITUITARY [J].
FISCHLI, W ;
GOLDSTEIN, A ;
HUNKAPILLER, MW ;
HOOD, LE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (17) :5435-5437
[10]   K-BINDING AND DEGRADATION OF [H-3] DYNORPHIN-A (1-8) AND [H-3] DYNORPHIN-A (1-9) IN SUSPENSIONS OF GUINEA-PIG BRAIN MEMBRANES [J].
GILLAN, MGC ;
ROBSON, LE ;
MCKNIGHT, AT ;
KOSTERLITZ, HW .
JOURNAL OF NEUROCHEMISTRY, 1985, 45 (04) :1034-1042