Neurotensin-related regulation of the postprandial lower-oesophageal-sphincter pressure.
BACKGROUND
Ingestion of food has been shown to modulate the lower-oesophageal-sphincter pressure (LESP). Fat is especially effective in decreasing the postprandial LESP. As there is good evidence that neurotensin (NT) is able to decrease the LESP, we conducted the present trial to determine whether NT could possibly be a mediator of the fat-induced decrease of the LESP.


METHODS
Six half-breed dogs were fitted for cervical side-to-side oesophagostomy to allow repeated oesophageal intubation; plasma NT immunoactivity was recorded during infusion of NT and after intragastric instillation of 200 ml of a fat solution. Experiments were repeated, with the specific NT antibody GN25 administered intravenously.


RESULTS
The optimal dose of NT required to simulate a postprandial situation was 50 pmol/kg/h. Infusion of this NT dose led to a statistically significant decrease of the LESP. Simultaneous administration of the NT antibody (immunoneutralisation) significantly inhibited this effect. Intragastric fat decreased the LESP and increased plasma NT. Immunoneutralisation of endogenously released NT led to an earlier restoration of baseline LESP, but this effect was not statistically significant.


CONCLUSIONS
NT and intragastric fat modulate the LESP. NT appears to mediate the postprandial, fat-induced decrease of the LESP. Research with specific NT-receptor antagonists is necessary to determine the exact role of NT and other regulatory peptides in this context.
Horstmann
O
O
Department of General Surgery, Georg August University, Robert Koch Strasse, G-37075, Göttingen, Germany. ohorstm@med.uni-goettingen.de
Nustede
R
R
Neufang
T
T
Lepsien
G
G
Becker
H
H
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D009496:Neurotensin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000502:physiology*; D019518:Postprandial Period; D011312:Pressure
D004041:Dietary Fats; D009496:Neurotensin