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

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

Research output: Contribution to journalArticle

14 Scopus citations

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

Keywords

  • cytoprotection
  • gastric
  • neurotensin
  • neurotensin-fragments

ASJC Scopus subject areas

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

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    Hernandez, D. E., Richardson, C. M., Nemeroff, C. B., 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