Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10.
Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduce 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-Arg9-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.
D000818:Animals; D001667:Binding, Competitive; D001833:Body Temperature Regulation; D005753:Gastric Mucosa / Q000294:innervation*; D008297:Male; D009496:Neurotensin / Q000502:physiology*; D010446:Peptide Fragments; D010454:Peptide Termination Factors / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology; D018028:Receptors, Neurotensin; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D010454:Peptide Termination Factors; D011956:Receptors, Cell Surface; D018028:Receptors, Neurotensin; D009496:Neurotensin; C041969:neurotensin (1-10); C041968:neurotensin (1-8); D011761:Pyrrolidonecarboxylic Acid