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 language | English |
|---|---|
| Pages (from-to) | 153-156 |
| Number of pages | 4 |
| Journal | Brain Research |
| Volume | 301 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 28 1984 |
| Externally published | Yes |
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Keywords
- cytoprotection
- gastric
- neurotensin
- neurotensin-fragments
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- Neuroscience(all)
Cite this
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 journal › Article
}
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 -