Phillips, S. F.

We compared responses of the gallbladder to graded intravenous infusions of cholecystokinin octapeptide (CCK-OP) in normal controls (n = 8) and patients with irritable bowel syndrome (IBS) with predominant constipation (n = 8) or diarrhea (n = 8). The doses of CCK-OP ranged from subphysiological (negligible contraction of the gallbladder) to supraphysiological (90% contraction of gallbladder and abdominal side effects) amounts. All gallbladders contracted progressively in response to CCK-OP, and a Weibull model (power exponential function) described precisely the gallbladder's response to CCK-OP. Patients with IBS responded differently from normal patients; those with constipation contracted their gallbladders more and those with diarrhea contracted less in response to the peptide. Gallbladders were also stimulated with a high-fat, liquid meal; all patients' gallbladders contracted, but clear differences between groups could not be demonstrated postprandially. The results suggest that the smooth muscle of the gallbladder in IBS has an abnormal sensitivity to CCK-OP, and the results support the concept that IBS can be a generalized abnormality of the smooth muscle of the digestive tract.

We describe here further observations on a novel motor phenomenon that can be recorded regularly from the canine ileum in the late postprandial period, i.e., when residue of a meal reaches the distal small bowel. We reported before that this unique pattern of motility consisted of intraluminal pressure waves at a frequency (20-24/min) much greater than that of the ileal slow wave. In the current experiments, we document that these intraluminal pressure waves coincide with contraction of the circular muscle layer, as recorded from serosal strain gauges. However, the cellular origin and propagation of these contractile events are still unclear. By studying dogs with ileal loops and those with an intact bowel, we conclude that this is a local response of the ileum to the arrival of nutrients in its lumen and that it is under cholinergic control. This report supports the concept that the ileum may be particularly sensitive to its local intraluminal environment.

We report here a novel motor phenomenon that we recorded from the canine terminal ileum in the postprandial period. In chronic models that allowed us to monitor myoelectrical activity and intraluminal pressure from the jejunum and distal ileum, we regularly saw in the ileum, but not in the jejunum, a rhythmic sequence of intraluminal pressure waves at a frequency of 19-24 cycles/min. This unusual motor pattern was rarely seen in the first 2 h after food and was essentially absent during fasting; it appeared reproducibly 1-4 h after food, at the time when chyme reached the ileum. The phenomenon was accompanied by spike bursts that were usually at the same rapid, rhythmic frequency, but the rate of the ileal slow wave persisted at the preprandial level (13-15/min). These findings further exemplify differences in the regulation of the motility between jejunum and ileum; moreover, the phenomenon highlights the capacity of the distal small intestine to response specifically to the nature of its luminal contents. This reaction of the ileum to the arrival of dietary residues is deserving of further study in the evaluation of the small bowel's response to a meal.

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

1. Perfusion of the human jejunum with low concentrations of glycine-conjugated bile acids in physiological solutions induced net fluid flow that varied between absorption and secretion, with only slight variation of the luminal osmotic and ionic milieu. 2. Transmucosal net flux rates for water and the principal ions were calculated. Regression analysis of the flux data was consistent with the concept of a ‘net transported fluid’ which was iso-osmotic with respect to the lumen, with a superimposed fixed net anion exchange unaffected by the rate or direction of bulk flow. 3. Recalculation of earlier data from comparable studies of the human colon showed similar relationships consistent with varying iso-osmotic bulk flow and fixed ion exchange, the latter differing from that found in the proximal bowel. 4. Studies were performed also in the human ileum. Variable iso-osmotic bulk flow was again encountered, but ion exchange was of a lower magnitude than in the jejunum or colon. Qualitatively, ion exchange in the ileum was intermediate between the jejunum and colon. 5. These analyses suggest that transmucosal bulk flow and ion exchange may be quantitatively and spatially independent processes. They provide support for the hypothesis that bulk flow may be intercellular (and hence extracellular), while ion exchange may take place across the luminal face of the mucosal cell. 6. Secretory agents, such as the dihydroxy bile acids, provide a useful means of analysing solute-solvent flow relationships in greatly differing bulk flow conditions with relatively stable physicochemical parameters.