Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10

Daniel E. Hernandez, Charles M. Richardson, Charles Nemeroff, Roy C. Orlando, Serge St-Pierre, Francis Rioux, Arthur J. Prange

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduced the incidence of cold-restraint stress (CRS)-induced gastric ulcers in rats. In this study we confirm the cytoprotective activity of central NT, and document structure-activity relationships for this effect of NT. When tested in a dose equimolar to 17.9 nmol of NT the NT analogs [Gln4]NT, d-Trp11-NT, and d-Arg8-NT were cytoprotective, whereas d-Arg[9-NT was not. Gonadotropin-releasing hormone (Gn-RH) and melanocyte-stimulating hormone-release inhibiting factor (MIF-1), two oligopeptides structurally unrelated to NT exhibited no cytoprotective efficacy in this paradigm. The C-terminal fragments of NT, xenopsin and NT8-13, and the N-terminal fragment NT1-6 were completely ineffective. Finally, NT1-8 and NT1-10, two N-terminal fragments of NT produced significant cytoprotective activity at this dose level. The cytoprotection afforded by NT1-8 and NT1-10, like that of NT, was dose-dependent with ED50's similar to that of NT (NT = 16.2 nmol, NT1-8 = 17.8 nmol and NT1-10 = 19.9 nmol). In conclusion, we demonstrate that smaller molecular weight forms of NT thought to be degradation products of NT can effectively exert biological effects.

Original languageEnglish
Pages (from-to)153-156
Number of pages4
JournalBrain Research
Volume301
Issue number1
DOIs
StatePublished - May 28 1984
Externally publishedYes

Fingerprint

Neurotensin
MSH Release-Inhibiting Hormone
xenopsin
Oligopeptides
Cytoprotection
Stomach Ulcer
Structure-Activity Relationship

Keywords

  • cytoprotection
  • gastric
  • neurotensin
  • neurotensin-fragments

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Hernandez, D. E., Richardson, C. M., Nemeroff, C., Orlando, R. C., St-Pierre, S., Rioux, F., & Prange, A. J. (1984). Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10. Brain Research, 301(1), 153-156. https://doi.org/10.1016/0006-8993(84)90414-1

Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10. / Hernandez, Daniel E.; Richardson, Charles M.; Nemeroff, Charles; Orlando, Roy C.; St-Pierre, Serge; Rioux, Francis; Prange, Arthur J.

In: Brain Research, Vol. 301, No. 1, 28.05.1984, p. 153-156.

Research output: Contribution to journalArticle

Hernandez, DE, Richardson, CM, Nemeroff, C, Orlando, RC, St-Pierre, S, Rioux, F & Prange, AJ 1984, 'Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10', Brain Research, vol. 301, no. 1, pp. 153-156. https://doi.org/10.1016/0006-8993(84)90414-1
Hernandez, Daniel E. ; Richardson, Charles M. ; Nemeroff, Charles ; Orlando, Roy C. ; St-Pierre, Serge ; Rioux, Francis ; Prange, Arthur J. / Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10. In: Brain Research. 1984 ; Vol. 301, No. 1. pp. 153-156.
@article{64b95e04143c497282e600da56f9029c,
title = "Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10",
abstract = "Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduced the incidence of cold-restraint stress (CRS)-induced gastric ulcers in rats. In this study we confirm the cytoprotective activity of central NT, and document structure-activity relationships for this effect of NT. When tested in a dose equimolar to 17.9 nmol of NT the NT analogs [Gln4]NT, d-Trp11-NT, and d-Arg8-NT were cytoprotective, whereas d-Arg[9-NT was not. Gonadotropin-releasing hormone (Gn-RH) and melanocyte-stimulating hormone-release inhibiting factor (MIF-1), two oligopeptides structurally unrelated to NT exhibited no cytoprotective efficacy in this paradigm. The C-terminal fragments of NT, xenopsin and NT8-13, and the N-terminal fragment NT1-6 were completely ineffective. Finally, NT1-8 and NT1-10, two N-terminal fragments of NT produced significant cytoprotective activity at this dose level. The cytoprotection afforded by NT1-8 and NT1-10, like that of NT, was dose-dependent with ED50's similar to that of NT (NT = 16.2 nmol, NT1-8 = 17.8 nmol and NT1-10 = 19.9 nmol). In conclusion, we demonstrate that smaller molecular weight forms of NT thought to be degradation products of NT can effectively exert biological effects.",
keywords = "cytoprotection, gastric, neurotensin, neurotensin-fragments",
author = "Hernandez, {Daniel E.} and Richardson, {Charles M.} and Charles Nemeroff and Orlando, {Roy C.} and Serge St-Pierre and Francis Rioux and Prange, {Arthur J.}",
year = "1984",
month = "5",
day = "28",
doi = "10.1016/0006-8993(84)90414-1",
language = "English",
volume = "301",
pages = "153--156",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10

AU - Hernandez, Daniel E.

AU - Richardson, Charles M.

AU - Nemeroff, Charles

AU - Orlando, Roy C.

AU - St-Pierre, Serge

AU - Rioux, Francis

AU - Prange, Arthur J.

PY - 1984/5/28

Y1 - 1984/5/28

N2 - Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduced the incidence of cold-restraint stress (CRS)-induced gastric ulcers in rats. In this study we confirm the cytoprotective activity of central NT, and document structure-activity relationships for this effect of NT. When tested in a dose equimolar to 17.9 nmol of NT the NT analogs [Gln4]NT, d-Trp11-NT, and d-Arg8-NT were cytoprotective, whereas d-Arg[9-NT was not. Gonadotropin-releasing hormone (Gn-RH) and melanocyte-stimulating hormone-release inhibiting factor (MIF-1), two oligopeptides structurally unrelated to NT exhibited no cytoprotective efficacy in this paradigm. The C-terminal fragments of NT, xenopsin and NT8-13, and the N-terminal fragment NT1-6 were completely ineffective. Finally, NT1-8 and NT1-10, two N-terminal fragments of NT produced significant cytoprotective activity at this dose level. The cytoprotection afforded by NT1-8 and NT1-10, like that of NT, was dose-dependent with ED50's similar to that of NT (NT = 16.2 nmol, NT1-8 = 17.8 nmol and NT1-10 = 19.9 nmol). In conclusion, we demonstrate that smaller molecular weight forms of NT thought to be degradation products of NT can effectively exert biological effects.

AB - Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduced the incidence of cold-restraint stress (CRS)-induced gastric ulcers in rats. In this study we confirm the cytoprotective activity of central NT, and document structure-activity relationships for this effect of NT. When tested in a dose equimolar to 17.9 nmol of NT the NT analogs [Gln4]NT, d-Trp11-NT, and d-Arg8-NT were cytoprotective, whereas d-Arg[9-NT was not. Gonadotropin-releasing hormone (Gn-RH) and melanocyte-stimulating hormone-release inhibiting factor (MIF-1), two oligopeptides structurally unrelated to NT exhibited no cytoprotective efficacy in this paradigm. The C-terminal fragments of NT, xenopsin and NT8-13, and the N-terminal fragment NT1-6 were completely ineffective. Finally, NT1-8 and NT1-10, two N-terminal fragments of NT produced significant cytoprotective activity at this dose level. The cytoprotection afforded by NT1-8 and NT1-10, like that of NT, was dose-dependent with ED50's similar to that of NT (NT = 16.2 nmol, NT1-8 = 17.8 nmol and NT1-10 = 19.9 nmol). In conclusion, we demonstrate that smaller molecular weight forms of NT thought to be degradation products of NT can effectively exert biological effects.

KW - cytoprotection

KW - gastric

KW - neurotensin

KW - neurotensin-fragments

UR - http://www.scopus.com/inward/record.url?scp=0021239642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021239642&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(84)90414-1

DO - 10.1016/0006-8993(84)90414-1

M3 - Article

C2 - 6329440

AN - SCOPUS:0021239642

VL - 301

SP - 153

EP - 156

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -