ROLE OF ENDOPEPTIDASE-3.4.24.16 IN THE CATABOLISM OF NEUROTENSIN, IN-VIVO, IN THE VASCULARLY PERFUSED DOG ILEUM

被引:43
作者
BARELLI, H
FOXTHRELKELD, JET
DIVE, V
DANIEL, EE
VINCENT, JP
CHECLER, F
机构
[1] UNIV NICE, INST PHARMACOL MOLEC & CELLULAIRE, CNRS, UPR 411, F-06560 VALBONNE, FRANCE
[2] MCMASTER UNIV, FAC HLTH SCI, SCH NURSING, HAMILTON L8N 3Z5, ON, CANADA
[3] CENS, DEPT INGN & ETUD PROT, STRUCT PROT SOLUT LAB, F-91191 GIF SUR YVETTE, FRANCE
[4] FAC HLTH SCI HAMILTON, DEPT NEUROSCI, HAMILTON L8N 3Z5, ON, CANADA
关键词
NEUROTENSIN; DEGRADATION; DOG ILEUM; ENDOPEPTIDASE; 24.15; 24.16; PEPTIDASES; PHOSPHODIEPRYL; 03; PRO-ILE;
D O I
10.1111/j.1476-5381.1994.tb13041.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The degradation of tritiated and unlabelled neurotensin (NT) following close intra-arterial infusion of the peptides in ileal segments of anaesthetized dogs was examined. 2 Intact NT and its catabolites recovered in the venous effluents were purified by chromatography on Sep-Pak columns followed by reverse-phase h.p.l.c. and identified by their retention times or by radioimmunoassay. 3 The half-life of neurotensin was estimated to be between 2 and 6 min. Four labelled catabolites, corresponding to free tyrosine, neurotensin (1-8), neurotensin (1-10) and neurotensin (1-11), were detected. 4 Neurotensin (1-11) was mainly generated by a phosphoramidon-sensitive cleavage, probably elicited by endopeptidase 24-11. 5 Two endopeptidase 3.4.24.16 inhibitors, phosphodiepryl 03 and the dipeptide Pro-Ile, dose-dependently potentiated the recovery of intact neurotensin. Furthermore, both agents inhibited the formation of neurotensin (1-10), the product that results from the hydrolysis of neurotensin by purified endopeptidase 3.4.24.16. In contrast, the endopeptidase 3.4.24.15 inhibitor Cpp-AAY-pAB neither protected neurotensin from degradation nor modifed the production of neurotensin (1-10). 6 Our study is the first evidence to indicate that endopeptidase 3.4.24.16 contributes to the catabolism of neurotensin, in vivo, in the dog intestine.
引用
收藏
页码:127 / 132
页数:6
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