Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid.
OBJECTIVE
The combination of duodenal lipid and gastric distention induces meal-like fullness followed by nausea in healthy subjects. The aim of this study was to assess the role of cholecystokinin (CCK) A receptors in these changes using a CCK-A antagonist loxiglumide.


METHODS
Twelve healthy subjects were studied on four occasions, during which either 0.9% saline or 20% Intralipid was infused intraduodenally on two occasions each (1 mL/min) while the proximal stomach was distended with air (100 mL/min). During each duodenal infusion, subjects received intravenous loxiglumide (10 mg.kg-1.h-1) on 1 day and placebo on the other. Intragastric pressure changes were recorded, and the subjects reported gastric sensations (fullness, nausea).


RESULTS
Loxiglumide did not influence gastric motility or sensitivity during duodenal saline infusion. Duodenal lipid reduced gastric tonic and phasic pressure activity during distensions and induced meal-like fullness and nausea; sensations were reported at similar volumes but lower intragastric pressures (P < 0.001 vs. saline). Loxiglumide partially restored gastric tonic and phasic activity during lipid infusion, reduced the occurrence of meal-like fullness and nausea, and increased the pressures at which sensations were reported (P < 0.001 vs. placebo).


CONCLUSIONS
CCK-A receptors are involved in the induction of meal-like fullness and nausea associated with intraduodenal lipid and gastric distention.
Feinle
C
C
Centre for Human Nutrition, Northern General Hospital, Sheffield, England.
D'Amato
M
M
Read
N W
NW
D000328:Adult; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D004386:Duodenum / Q000187:drug effects*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005260:Female; D013271:Gastric Dilatation / Q000378:metabolism / Q000503:physiopathology*; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D009325:Nausea / Q000503:physiopathology; D011312:Pressure; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012677:Sensation; D013270:Stomach / Q000503:physiopathology*
D005217:Fat Emulsions, Intravenous; D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D011377:Proglumide