Plasma Concentrations Of Motilin Research Articles

Delayed Gastric Emptying and Intestinal Hormones following Pancreatoduodenectomy

Background/Aims: Delayed gastric emptying (DGE) is frequently reported in patients following pancreatoduodenectomy (PD). The present study tested the hypothesis that gastrointestinal hormones known to effect gastric emptying contribute to DGE in patients after PD. Methods: Patients with (delayed, n = 9) or without clinical signs of DGE (non-delayed, n = 22) after PD were investigated. Plasma concentrations of motilin, glucagon-like peptide-1 (GLP-1), neurotensin, and peptide YY (PYY) and the gastric emptying rate (GER), assessed by the paracetamol absorption method were measured after a liquid meal on postoperative day 11. Results: Days with a nasogastric tube (p < 0.01), days until solid food was tolerated (p < 0.05), and hospital stay (p < 0.001) were increased in delayed compared to non-delayed patients. The total and incremental integrated peptide responses of motilin and GLP-1 were similar, but the responses of neurotensin and PYY were reduced, in delayed compared to non-delayed patients, whether considered on clinical grounds or by measured GER (p < 0.05–0.005). Conclusion: Neurotensin and PYY slow the rate of gastric emptying in humans. Therefore, our findings suggest that reduced hormone responses were the consequence of DGE arising from delayed delivery of nutrients to the distal intestine where the endocrine cells secrete neurotensin and PYY reside.

Effect of Duodenectomy on Gastric Motility and Gastric Hormones in Dogs

To test the hypothesis that the duodenum is required to coordinate interdigestive insulin secretion with gastrointestinal motility and to determine whether duodenectomy alters the interdigestive cycles of plasma motilin and insulin levels and their relations to insulin secretion and motility. Adult mongrel dogs were chronically implanted with force transducers in the stomach, duodenum, and upper jejunum to monitor contractile activity. Eight healthy mongrel dogs were divided into control and duodenectomized dogs. Insulin secretion, gastrointestinal motility, and plasma concentrations of motilin during the interdigestive period were measured in normal and duodenectomized dogs. After duodenectomy, no obvious phase III contractions were seen in the gastric antrum, but migrating phase III contractions were seen in the upper jejunum. The plasma motilin concentration did not fluctuate as it does in normal dogs, and remained low. After duodenectomy, insulin secretory cycles were not coordinated with either cycles of interdigestive motility or the plasma concentration of motilin. Exogenous motilin administration stimulated endogenous insulin release significantly compared with saline-treated controls. The contractile response of the stomach to exogenous motilin after duodenectomy was similar to that of intact dogs. Duodenectomy disrupts the relation between cycles of both interdigestive gastrointestinal motility and insulin secretion. These effects of duodenectomy may be attributable to interruption of the duodenopancreatic neural connections, hormonal abnormalities, or loss of vagus-sensitive humoral factors. The duodenum, which stores motilin, seems to play an important role in the relations between gastric migrating motor complexes and the concomitant increase of insulin secretion in fasted dogs. The mechanism responsible for the effect of motilin in both duodenectomized and normal dogs may involve a cholinergic pathway.

Intraduodenal neuropeptide levels, but not plasma levels, vary in a cyclic fashion with the migrating motor complex.

The neurohormonal control of the migrating motor complex (MMC) is not fully understood. The hypothesis of the present study was that neuropeptide levels might vary with the different phases of the MMC and that a similar variation might be found in the secretions of the gastrointestinal tract. Thus, plasma and intraduodenal concentrations of vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and neurokinin A (NKA) were determined by radioimmunoassay every 10 min during two complete MMC cycles in eight male subjects. For comparison, plasma motilin (MOT) concentrations were measured. Plasma concentrations of MOT (mean peak value +/- SEM; 39 +/- 6 pmol L-1), but none of the neuropeptides studied, showed a cyclic variation in plasma with the different phases of the MMC. Peak intraduodenal concentrations of VIP (79 +/- 23 pmol L-1), SOM (2437 +/- 432 pmol L-1) and SP (718 +/- 326 pmol L-1) occurred at or at the time point before the onset of phase III of the MMC. No such correlation was observed for NKA. These results demonstrate that intraduodenal but not plasma concentrations of the neuropeptides VIP, SOM and SP show an association with phase III of the MMC. The biological relevance of this finding is yet unclear, but the results raise the possibility that gut neuropeptides may regulate fasting motility through a luminal release.

Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants.

In adults, migrating motor complexes (MMCs) appear to be partially under hormonal modulation by motilin and pancreatic polypeptide. Preterm infants do not exhibit MMCs until 32 wk of gestation. Although plasma concentrations of motilin are similar in infants and adults, it is not known if actual hormonal modulation of MMCs is present in infants. In the first study we assessed whether plasma concentrations of motilin and pancreatic polypeptide surge with the occurrence of MMCs in term infants. In the second study we assessed whether erythromycin, a motilin receptor agonist, could induce migrating motor activity in preterm and term infants. In the first study we recorded motor activity in nine term infants who had never been fed. We determined plasma concentrations of motilin and pancreatic polypeptide in the presence and absence of MMCs. In the second study we gave the motilin agonist erythromycin intragastrically to 21 infants at a range of 24-42 wk of gestation to assess whether migrating activity could be induced via the motilin receptor. In the first study, plasma concentrations of motilin were similar during the presence and absence of MMCs, as were plasma concentrations of pancreatic polypeptide. In the second study, the administration of erythromycin induced the appearance of migrating activity in 7 of 14 infants who were older than 32 wk but in none of the infants who was younger than 32 wk. Although the motilin receptor appears to be functionally present beyond 32 wk of gestation, as assessed by in indirect pharmacologic challenge, hormonal modulation of migrating activity in the neonate by plasma motilin and pancreatic polypeptide is absent.

Disseminated rectal carcinoid tumor with production of immunoreactive motilin.

This report presents a patient with a rectal carcinoid tumor of small size ( 14 mm in diameter), with typical growth pattern, localized in the mucosa. Despite these microscopically good prognostic features the patient died from metastatic disease 30 months later. The tumor had an unusual hormone profile with main secretion of immunoreactive motilin and serotonin. Immunocytochemically these substances were localized in separate tumor cell populations; the majority of tumor cells were motilin-immunoreactive and a minority were serotonin-immunoreactive. The patient was first treated interventionally by hepatic arterial embolizations and later medically with octreotide. The treatment resulted in long periods of good palliation related to reduced levels of tumor markers and weight gain. The plasma concentrations of motilin were analyzed with a N-terminal-specific assay before and during treatment.

Interdigestive gastroduodenal motility and cycling of putative regulatory hormones in severe obesity.

The aim of the present study was to evaluate interdigestive gastrointestinal motility and its coordination with plasma concentrations of motilin and pancreatic polypeptide (PP) in 14 patients with severe obesity and in 10 control subjects with normal body weight. Motor activity of the stomach, duodenum, and proximal jejunum was recorded by using an eight-lumen catheter. Blood samples were drawn for determination of interdigestive motilin and PP plasma concentrations. We observed no difference in total duration of the migrating motor complex (MMC) or of phases I, II, or III of the MMC. Gastric phase-III activity occurred less frequently in severely obese patients (only 15% originating in the stomach) than in controls (65%; p less than 0.01). Plasma motilin concentrations were decreased in obese patients in phase I (127 +/- 17 pg/ml in controls versus 87 +/- 10 pg/ml in obese), in phase II (189 +/- 26 pg/ml controls versus 134 +/- 15 obese) and in phase III (195 +/- 29 pg/ml controls versus 153 +/- 28 pg/ml obese). Peak motilin release occurred in synchrony with phase-III activity and was greater in controls than in obese patients. Plasma PP concentrations did not differ from those of controls during any phase of the MMC. These results further suggest a potential role for motilin in regulating gastrointestinal motor activity and indicate a potential defect in this regulatory mechanism in severe obesity. Whether the relationship between disordered motor activity and motilin release is etiologic with regard to the pathophysiology of obesity remains to be determined.

Battery powered angioplasty.

The development of the effects of a human milk feed on plasma concentrations of motilin, neurotensin, gastric inhibitory polypeptide, enteroglucagon, gastrin, and secretin were studied in 158 healthy preterm neonates (mean gestation 33 1/2 weeks) at mean postnatal ages of 2 1/2, 6, 13, or 24 days. Pronounced progressive changes occurred in postprandial hormone responses; these were absent or small in the first days of life and were large by age 24 days. These changes may have important consequences in the adaptation to postnatal life.

Role of the duodenum in the control of canine gastrointestinal motility

This study was designed to determine the role of the duodenum in controlling the interdigestive migrating motor complex of the canine stomach and small intestine. The motility patterns of 4 dogs were studied before and after resection of the entire duodenum with reimplantation of bile and pancreatic ducts. Before duodenectomy, plasma concentrations of motilin and pancreatic polypeptide varied cyclically with the migrating motor complex. After duodenectomy, the migrating motor complex was abolished in the stomach in 3 of the 4 dogs during fasting. The other dog demonstrated what appeared to be an intermittent cyclic increase in gastric contractile activity, but with markedly abnormal characteristics and at irregular intervals. The jejunal migrating motor complex continued to cycle after duodenectomy in all 4 dogs, but the mean period was shorter than before duodenectomy (83 min vs. 147 min, p < 0.01). Duodenectomy abolished the cyclic variations of plasma motilin and pancreatic polypeptide and lowered the concentration of both peptides during all phases. This study suggests that the duodenum plays an important role in the initiation of the gastric migrating motor complex and in the coordination of interdigestive gastrointestinal motor activity, possibly by the release of motilin.

Human pancreatic secretion during phase II antral motility of the interdigestive cycle.

We determined if changes in the irregular motor activity of phase II, the dominant motility phase in awake fasting humans, are associated with fluctuations in pancreatic secretion by intubating the upper gastrointestinal tract of 15 healthy humans and recording antral and duodenal motility and obtaining duodenal samples for one or two interdigestive motility cycles. Antral phase II activity was graded as having low, intermediate, or high frequency of contractions and related to duodenal trypsin output and plasma concentrations of motilin and human pancreatic polypeptide (HPP), a marker of vagal cholinergic tone. Low, intermediate, and high phase II motor activities were significantly associated with trypsin outputs (U/10 min; mean +/- SE) of 576 +/- 137, 1,441 +/- 225, and 3,621 +/- 521, respectively (P less than 0.001). Plasma motilin levels did not vary with the grades of phase II motility (P greater than 0.1), but levels of plasma HPP and the grades of phase II motility were positively correlated (P less than 0.001). The close correlation among motility, pancreatic secretion, and plasma HPP during phase II suggests that vagal cholinergic pathways are involved in the common regulatory mechanism controlling phase II interdigestive motility and pancreatic secretion.

Motilin in Plasma and Tumor Tissues from Patients with the Carcinoid Syndrome Possible Involvement in the Increased Frequency of Bowel Movements

Motilin, normally present in a specific cell type in the upper small intestine, is believed to have a physiologic role in initiating the interdigestive migrating motor complex. Motilin may play a pathophysiologic role in the diarrhea in the irritable bowel syndrome, the dumping syndrome, chronic liver disease, and chronic renal failure. Furthermore, increased frequency of bowel movements is an important symptom in patients with the carcinoid syndrome. We have studied 73 patients with metastatic carcinoid tumors with regard to stool frequency and plasma concentration of motilin and neuropeptide K (NPK) and diurnal urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). Thirty-eight (52%) of the 73 patients had elevated (greater than 126 pmol/l) plasma concentrations of motilin, whereas 59 (81%) of the patients had diarrhea. The increased frequency of bowel motions correlated significantly (p less than 0.01) with the plasma concentrations of motilin, whereas no significant correlation with 5-HIAA and NPK was found. High-performance liquid chromatography of plasma extracts showed a single component eluting in the position of synthetic porcine motilin. However, extracts from five carcinoid tumors did not contain any significant levels of motilin. Carcinoid tumors are known to contain and secrete several biologically active substances such as serotonin, histamine, prostaglandins, and tachykinins, which are likely to cause disturbances of intestinal secretion and motility, which in turn might release motilin from the motilin-containing cells of the small intestine. The increased motilin levels might then participate in a vicious diarrhea circle together with the other agents.

Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog.

We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.

Plasma motilin, gastrin, and enteroglucagon and feeding in the human newborn.

Plasma concentrations of motilin, gastrin, and enteroglucagon were measured in cord blood and during the first 24 days of life before feeding in 45 term and 63 preterm, healthy infants. Levels of these hormones rose steeply after birth, reaching concentrations that were much higher than those in fasting adults. These increases in hormone concentration were not present in a group of 10 preterm infants who had received only intravaenous dextrose from birth because of hyaline membrane disease. Our findings suggest that early enteral feeding may trigger the postnatal increase in plasma concentrations of gut hormones and that this could play an important role in the physiologaical adaptations to extrauterine nutrition.

Development of gut hormone responses to feeding in neonates.

The development of the effects of a human milk feed on plasma concentrations of motilin, neurotensin, gastric inhibitory polypeptide, enteroglucagon, gastrin, and secretin were studied in 158 healthy preterm neonates (mean gestation 33 1/2 weeks) at mean postnatal ages of 2 1/2, 6, 13, or 24 days. Pronounced progressive changes occurred in postprandial hormone responses; these were absent or small in the first days of life and were large by age 24 days. These changes may have important consequences in the adaptation to postnatal life.