Sensitivities of human jejunum, ileum, proximal colon, and gallbladder to cholecystokinin octapeptide

Abstract

We compared in humans simultaneous motor responses of the jejunum, ileum, proximal colon, and gallbladder (GB) to intravenous cholecystokinin octapeptide (CCK-OP). To gauge the physiological relevance of the doses of CCK-OP, intestinal motility and GB contraction were also quantified after a fatty meal. Eight healthy volunteers participated in both experiments. Six graded, 30-min intravenous infusions had a mean range of 2.2 to 73.2 pmol X kg-1 X h-1 of CCK-OP; these spanned from subphysiological (negligible contraction of GB) to pharmacological (producing intestinal symptoms and a 70-99% contraction of GB) levels. CCK-OP inhibited interdigestive cycles of motility, though in some persons fasting patterns persisted with doses of CCK-OP, which produced up to 50% reduction in GB volume. Motility indices of the ileum and proximal colon responded to CCK-OP by decreasing initially but then increasing with larger doses; motility of the jejunum increased gradually at all doses. Judged by the gallbladder's response to food (reduction in volume down from 74 to 29% of original volume), the physiological range of infused CCK-OP was approximately 5-16 pmol X kg-1 X h-1. Within this range of doses of CCK-OP, motility of the jejunum increased, whereas motility of the proximal colon was reduced. These data are consistent with CCK being a "physiological" mediator of intestinal motility in humans; responses of the intestine to the peptide appear to vary regionally.