| I have shown that integrity of bilateral vagal innervation is essential for expression of lower esophageal sphincter (LES) and stomach motility, in the fasted state. In addition, the intense contractions comprising phase III of the fasting migrating motor complex (MMC) in the upper small bowel do not require vagal integrity, whereas phase II does. Therefore, fasting contractile activity in the upper small bowel is controlled by two neural pathways, one of which is vagal.; Feeding replaces the MMC with continuous, low-amplitude activity termed the postprandial, or feeding pattern, during which time phase III activity is not observed. I have shown that postprandial activity in the upper gastrointestinal tract is vagally controlled. In addition, feeding masks, but does not stop the "clock" initiating the MMC.; I have demonstrated that the MMC-associated peaks in gastrin and pancreatic polypeptide (PP) are vagally mediated. However, motilin release is controlled by a major non-vagal cholinergic excitatory pathway, and a minor vagal inhibitory pathway. PP infusion approximating peak fasting levels has no effect on the MMC or motilin, indicating that fasting PP release does not initiate the MMC.; PP infusion producing postprandial concentrations does not initiate postprandial activity, or affect phase II motility. However, it does abolish phase III of the MMC and its associated peak in motilin. Thus, pancreatic polypeptide does not cause the feeding pattern, as has been previously proposed, but it may be responsible for the postprandial inhibition of phase III.; Motilin has been proposed as the initiator of phase III. I have shown that porcine motilin initiates phase III-like motility, and a delayed peak in canine motilin. These effects of motilin injection are dose-dependent, are affected by manipulation of vagal integrity, and depend on cholinergic innervation. The latter findings were also observed in the control of spontaneous motility and motilin release. The fact that motilin both initiates phase III-like activity, and causes additional motilin release, indicates that it may provide positive feedback amplification of phase III of the MMC.; Finally, I have proposed a hypothetical model of gastrointestinal motility control that integrates my results with those of others. |
