EFFECT OF CHOLECYSTOKININ ON LOWER ESOPHAGEAL SPHINCTER PRESSURE AND TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXATIONS IN HUMANS

The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the numbe r of reflux episodes was investigated in six healthy subjects. LOS pre ssure was recorded on four separate occasions during continuous intrav enous 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 infusi on, 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 res pectively starting from 30 minutes. LOS pressure did not change signif icantly 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 pr essure 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 durin g infusion of CCK-33 at a dose of 1.0 IDU.kg(-1).h(-1). In addition, o esophageal motility and pH were recorded simultaneously in these six s ubjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) comb ined with continuous intravenous infusion of saline or CCK-33 at a dos e of 1.0 IDU.kg(-1).h(-1) Plasma CCK concentrations did not change dur ing the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infus ion of CCK. The number of transient LOS relaxations increased signific antly in the first hour during administration of the gastric load comp ared with fasting levels, both during saline infusion (fasting: 1.7 (0 .6)/h, Ist 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 numbe r of transient LOS relaxations fell to fasting levels in both experime nts. No significant differences were observed in the number and type o f transient LOS relaxations, mechanism of gastro-oesophageal reflux, o r duration of acid exposure between the two experiments. It is conclud ed 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.