Role of CCK(A) receptors in postprandial lower esophageal sphincter function in morbidly obese subjects.
To reduce weight, some morbidly obese patients are treated with an intragastric balloon, often resulting in increased reflux symptoms. As transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism underlying reflux and can be reduced by cholecystokinin-A (CCK(A)) blockade, we hypothesized that the CCK(A)-receptor antagonist loxiglumide could reduce gastroesophageal reflux in these subjects. Postprandial manometric studies were performed in 12 obese subjects during infusion of placebo or loxiglumide. Before balloon placement, loxiglumide did not significantly reduce the rate of TLESRs but attenuated the postprandial decrease in LES pressure. After 10 weeks of balloon treatment, loxiglumide significantly reduced the rate of TLESRs. Postprandial LES pressure was significantly increased, whereas the meal-induced decrease in LES pressure was absent. Neither loxiglumide nor balloon placement affected gastroesophageal reflux. In conclusion, CCK(A) receptors play an important role in post-prandial LES pressure decrease and are involved in the reflex pathway underlying the triggering of TLESRs, at least after balloon placement.
Hirsch
D P
DP
Division of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
Mathus-Vliegen
E M H
EM
Holloway
R H
RH
Fakhry
N
N
D'Amato
M
M
Boeckxstaens
G E E
GE
D000328:Adult; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008365:Manometry; D008875:Middle Aged; D009767:Obesity, Morbid / Q000503:physiopathology*; D019518:Postprandial Period / Q000502:physiology*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000502:physiology*
D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D011377:Proglumide