Involvement of cholecystokininA receptors in transient lower esophageal sphincter relaxations triggered by gastric distension.
OBJECTIVE
Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastroesophageal reflux. In the present study we evaluated the effect of loxiglumide, a specific cholecystokininA (CCKA)-receptor antagonist, on the occurrence of TLESRs evoked by gastric distension.


METHODS
Eight healthy subjects underwent esophageal manometry using a 10-lumen sleeve assembly during placebo or loxiglumide (10 mg/kg/h) in a randomized double-blind order. Gastric distension was induced by inflation of 400 ml of air.


RESULTS
Basal lower esophageal pressure (LESP) and swallow-induced relaxation were not affected by loxiglumide. Loxiglumide significantly reduced the number of TLESRs, from 11.5 (5.8-18.3) to 6.0 (3.3-14.3) during the total recording period of 1 h, and from 5.5 (4.25-7.5) to 2.0 (0.5-6.8) during the first 15 min. The number of common cavities was significantly decreased by loxiglumide, from 8.0 (4.0-20.0) to 5.0 (2.0-7.8). TLESRs represented the main mechanism (60% during placebo, 74% during loxiglumide) underlying common cavities, followed by swallow-induced relaxation.


CONCLUSIONS
Loxiglumide significantly reduces the number of TLESRs triggered by gastric distension without interfering with swallow-related relaxation of the lower esophageal sphincter, suggesting the involvement of CCKA receptors in the reflex pathway mediating TLESRs.
Division of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
G E
GE
Boeckxstaens
D P
DP
Hirsch
N
N
Fakhry
R H
RH
Holloway
M
M
D'Amato
G N
GN
Tytgat
D000328:Adult; D003679:Deglutition / Q000502:physiology; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000503:physiopathology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D008365:Manometry; D010528:Peristalsis / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000502:physiology; D013270:Stomach / Q000502:physiology*
D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D011377:Proglumide