Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors.
OBJECTIVE
Exogenous cholecystokinin (CCK) decreases lower esophageal sphincter (LES) pressure and increases transient LES relaxations (TLESRs) in humans. The aims of this study were to determine whether endogenous CCK increases gastroesophageal reflux in humans and whether this is a direct effect on the LES.


METHODS
Esophageal pH, LES pressure, and gallbladder volume were measured in 8 healthy volunteers after ingestion of a 181-kcal meal alone or adding 12 g cholestyramine to increase endogenous CCK release. In 7 additional volunteers, the effect of cholestyramine was studied during intravenous perfusion of saline or the CCK-A receptor antagonist loxiglumide. In circular LES strips from 9 transplant donors, we measured the effect of CCK-8 (10(-11) to 3 x 10(-8) mol/L) on basal tension and on electrical field-induced relaxation.


RESULTS
Cholestyramine increased gallbladder emptying, reflux episodes, TLESRs, and time of esophageal pH of <4. Loxiglumide inhibited postprandial gallbladder emptying, reflux episodes, TLESRs, and time of pH of <4 and prevented the decrease in LES pressure induced by cholestyramine. In vitro, CCK-8 contracted LES strips through a tetrodotoxin-insensitive pathway but did not modify electrical field-induced LES relaxations.


CONCLUSIONS
Endogenous CCK enhances postprandial gastroesophageal reflux in humans by increasing the rate of TLESRs and reduces postprandial LES pressure. These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle.
Laboratori d'Investigació Gastrointestinal, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
P
P
Clavé
A
A
González
A
A
Moreno
R
R
López
A
A
Farré
X
X
Cussó
M
M
D'Amato
F
F
Azpiroz
F
F
Lluís
D000328:Adult; D002766:Cholecystokinin / Q000378:metabolism / Q000502:physiology*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D004435:Eating; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004947:Esophagus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005704:Gallbladder / Q000502:physiology; D005764:Gastroesophageal Reflux / Q000503:physiopathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D002792:Cholestyramine Resin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide; D012844:Sincalide