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. 2001 Mar;48(3):347–355. doi: 10.1136/gut.48.3.347

Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia

C Feinle 1, O Meier 1, B Otto 1, M D'Amato 1, M Fried 1
PMCID: PMC1760121  PMID: 11171824

Abstract

BACKGROUND/AIMS—We aimed to evaluate the role of fat and cholecystokinin (CCK) in the pathophysiology of functional dyspepsia (FD) by investigating symptoms and plasma CCK levels following increasing doses of duodenal lipid during gastric distension, and the effect of CCK-A receptor blockade.
SUBJECTS/METHODS—In study A, six FD patients were studied on three occasions during duodenal infusion of saline or lipid (1.1 (L-1) or 2 kcal/min (L-2)) and proximal gastric distensions. Six healthy subjects were also studied as controls during L-2 only. In study B, the effect of the CCK-A antagonist dexloxiglumide (5 mg/kg/h) on L-2 induced symptoms was studied in 12 FD patients. Changes in gastric volume at minimal distending pressure and plasma CCK (study A) were assessed, gastric distensions were performed using a barostat, and dyspeptic symptoms were monitored.
RESULTS—Lipid increased gastric volume compared with saline (ΔV (ml): saline 15 (20), L-1 122 (42), L-2 114 (28)) in patients and even more so in controls (221 (37); p<0.05). During distensions, symptoms were greater during L-2 than during saline or L-1, and greater in patients than in controls, while gastric compliance was smaller in patients than in controls (p<0.05). Lipid increased plasma CCK levels in patients and controls (p>0.05). Dexloxiglumide abolished the increase in gastric volume (ΔV (ml): dexloxiglumide 17 (9), placebo 186 (49)) and dyspeptic symptoms (sum of scores: dexloxiglumide 24 (7), placebo 44 (19)) during duodenal lipid infusion. Dexloxiglumide also reduced gastric compliance (ml/mm Hg: dexloxiglumide 51 (7), placebo 72 (11)) and symptoms (sum of scores: dexloxiglumide 101 (17), placebo 154 (21)) during gastric distension.
CONCLUSION—CCK-A receptors are involved in the generation of dyspeptic symptoms by duodenal lipid during gastric distension.


Keywords: functional dyspepsia; duodenal lipid; cholecystokinin; dyspeptic symptoms

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Figure 1  .

Figure 1  

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Experimental protocols for study A (dose-response study) and study B (cholecystokinin (CCK)-A receptor blockade). To determine the relationship between the lipid dose administered and severity of dyspeptic symptoms, six patients were studied on three occasions each, receiving duodenal infusion of 0.9% saline, or 10% or 20% lipid. Six healthy subjects were studied after infusion of 20% lipid only. During infusions, changes in gastric volume were assessed and the proximal stomach was distended in steps of 1 mm Hg/min while symptoms were monitored and plasma CCK levels determined. In study B, 12 patients were studied twice to investigate the effect of CCK-A receptor blockade with dexloxiglumide on the symptomatic and gastric volume responses evoked by duodenal infusion of 20% lipid and gastric distension. VAS, visual analogue scale.

Figure 2  .

Figure 2  

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Gastric volume responses to duodenal infusion of isotonic saline, or 10% or 20% lipid in patients with functional dyspepsia (FD) and to infusion of 20% lipid in healthy subjects (HS) (n = 6).

Figure 3  .

Figure 3  

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Plasma cholecystokinin (CCK) levels (baseline levels normalised) obtained in response to duodenal infusion of isotonic saline, or 10% or 20% lipid (n=6) in patients with functional dyspepsia (FD) and healthy subjects (HS) before and during gastric distensions. The value at t=20 minutes in healthy subjects is due to one outlier. D1, distension 1; D2, distension 2. 

Figure 4  .

Figure 4  

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Scores for dyspeptic symptoms during duodenal infusion of isotonic saline, or 10% or 20% lipid in patients with functional dyspepsia (FD) and 20% lipid in healthy subjects (HS) (A) and when infusions were combined with gastric distension (B).

Figure 5  .

Figure 5  

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Scores for dyspeptic symptoms during duodenal infusion of 20% lipid given with intravenous placebo or dexloxiglumide in patients with functional dyspepsia (A) and when infusions were combined with gastric distension (B).

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