title: Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans.
abstract: The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h-1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load.
authors.affiliation: Department of Gastroenterology-Hepatology, University Hospital of Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Ledeboer
authors.forename: A A
authors.initials: AA
authors.lastname: Masclee
authors.forename: M R
authors.initials: MR
authors.lastname: Batstra
authors.forename: J B
authors.initials: JB
authors.lastname: Jansen
authors.forename: C B
authors.initials: CB
authors.lastname: Lamers
mesh_terms: D000328:Adult; D002766:Cholecystokinin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D005764:Gastroesophageal Reflux / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects*; D011312:Pressure
chemical_list: D002766:Cholecystokinin