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  • 1
    Electronic Resource
    Electronic Resource
    Species-specific effects of neurotensin on gallbladder contractionin vitro (1989)
    Springer
    Digestive diseases and sciences 34 (1989), S. 21-26 
    Details
    ISSN: 1573-2568
    Keywords: neurotensin ; gallbladder contraction ; sphincter of Oddi ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously shown that an in vivoadministration of neurotensin (NT) stimulates contraction of dog gallbladder (GB), but produces dilatation of GB in humans. The objective of this study was to examine the effect of NT on human, dog, guinea pig, and rabbit GB in vitro,in order to delineate direct versus indirect actions of NT in different species and to evaluate the structure-activity relationships of NT. The effect of NT on the canine sphincter of Oddi (SOD) was also examined in vitro.Isolated longitudinal strips of GB from the four species given above and SOD from dogs were suspended in oxygenated Krebs buffer, and the isometric tension responses to various doses of NT, NT 8–13, NT 1–11, and xenopsin (XP) were determined. All the NT homologs, except NT 1–11, stimulated contraction of the dog GB and SOD in a dose-dependent manner. NT also caused dose-related stimulation of GB contraction from guinea pigs but did not stimulate or depress the contractile activity of human and rabbit GB strips. These results suggest that NT action on GB contraction is species-specific. Tetrodotoxin did not modify the contraction of dog GB and SOD in response to NT, indicating that NT mediates its contractile effects directly. The relaxing effect of NT on GB of humans in vivo,as previously reported by us, thus appears to be an indirect action. The fact that structural changes in the NT molecule resulted in marked changes in the biological activity of NT on GB activity in dogs indicates that the effects of NT on dog GB contraction are probably mediated through binding of NT to specific receptors that requires both the C-terminal amino group and the two C-terminal amino acids to produce a contractile response. Based on these results, we suggest that NT may participate in the regulation of GB and SOD contraction in dogs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01536149
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of oral fat on plasma levels of neurotensin and neurotensin fragments in humans (1990)
    Springer
    Digestive diseases and sciences 35 (1990), S. 200-204 
    Details
    ISSN: 1573-2568
    Keywords: high-pressure liquid chromatography ; neurotensin ; peptide ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of ingestion of fat (Lipomul 1 g/kg) on the circulating levels of neurotensin (NT1–3) and amino-terminal fragments (NT1–8, NT1–11) and carboxy-terminal fragment (NT8–13) of NT were investigated in six healthy male volunteers. NT and NT fragments were extracted from plasma collected at 0, 15, 30, and 60 min after ingestion of fat, and the plasma levels of NT1–13 and NT fragments were characterized using high-pressure liquid chromatography and radioimmunoassay techniques. Significant elevations of plasma levels of NT1–8, NT1–11, and NT1–13 were observed at 15, 30, and 60 min after fat ingestion. The maximum elevations were 273% for NT1–8, 234% for NT1–11, and 54% for NT1–13. NT8–13 levels failed to rise significantly when compared to basal levels. These findings indicate that both the aminoterminal and carboxyterminal fragments of NT are either released along with intact NT or are formed as metabolites from NT1–13 in response to ingestion of fat in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01536763
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo (1989)
    Springer
    Investigational new drugs 7 (1989), S. 131-138 
    Details
    ISSN: 1573-0646
    Keywords: polyamines ; cancer ; 2-deoxy-D-glucose ; α-difluoromethylornithine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. α-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170849
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    Paper (German National Licenses)
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