Plasma Motilin Levels Research Articles

The ontogeny of the small intestinal epithelium.

The primary factors in feeding premature infants are dependent on the development and maturation of digestion and absorption. The maturation of digestive and absorptive functions of carbohydrates, proteins, fats, minerals, and vitamins in the young premature infant were determined in relation to availability of hydrolytic enzymes, such as lipases, proteases, amylases, glucosidases, and lactase. The feeding is dependent on the ability of the premature infant to secrete salivary enzymes, gastric acid, pepsin, pancreatic exocrine enzymes, the presence of enterohepatic circulation, and the hydrolytic and absorptive capacity of the entercocyte. To evaluate the complexity of the gut maturation process, we proposed a unified concept where the ontogeny of the gastrointestinal system is the result of the following four major determinants: genetic endowment, intrinsic developmental and biological clock, endogenous regulatory mechanisms, and environmental influences. The developmental clock represents a predetermined temporal sequence of happenings in ontogeny that is inherently controlled. By 20 weeks of gestation, the anatomic differentiation of the fetal gut has progressed to the extent that it resembles that of a newborn. Secretory and absorptive functions, however, develop at different rates; the intestinal absorptive process is only partially available before 26 weeks of gestation, whereas gastric and pancreatic secretion is only basal and can be stimulated only partially even in the full-term newborn period. Regulatory mechanisms control the expression of the genetic endowment at various stages in gastrointestinal development. Neural-hormonal factors play major roles in the ontogeny of the gut. Adrenalectomy, hypophysectomy, and thyroidectomy delay the development of the gut. Administration of glucocorticoids or thyroxine at the critical stage in maturation causes early appearance of enzymes within the intestine. Other hormones that are potentially important in regulating gastrointestinal development include cholecystokinin, gastrin, secretin, which have trophic effects on the gastrointestinal tract, and insulin, insulin-like growth factors, and epidermial growth factor. The development of gastrointestinal secretory function, particularly in response to hormonal stimulation, has received considerable attention. The degree of response of the target cell is determined not only by the amount of effective hormone reaching it but also by the number and affinity of receptors on its surface. Human newborns have high levels of gastrin in their sera, yet have low acid output. Exogenous gastrin is an ineffective stimulant despite the presence of seemingly "anatomically developed" parietal cells. It seems that neither endogenous nor exogenous gastrin has an effect on the target cell. If one accepts the role of circulating gastrin levels in the regulation of its own receptor, one can hypothesize the absence of a regulatory effect of gastrin in the newborn period. It was shown that hormonal regulation of migrating activity by motilin is also absent in the preterm and term infant. Plasma levels of motilin in neonates are comparable to those found in adults, but migrating motor complexes occur in the absence of cycling of plasma concentrations. Interestingly, however, the motilin receptor appears to be present. In conclusion, the feeding mode content, concentration, and volume of the very young premature infant can be assessed by the development of digestive and absorptive capacity and gut motility. The concomitant changes in gut hormones and regulatory peptides during ontogeny and feeding will add a new dimension in the understanding of when, what, and how to feed the very young premature infant.

Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

Background—Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying.Aims—To explore the effect...

Effect of cerebroventricular perfusion of bombesin on gastrointestinal myoelectric activity

The effect of intracerebroventricular (i.c.v.) perfusion of bombesin (BBS) on the interdigestive migrating myoelectric complex (MMC) activity was examined in conscious dogs with electrodes implanted on the stomach and small intestine. Cannulas and a catheter were chronically positioned in the lateral and fourth cerebral ventricles, respectively. i.c.v. perfusion of BBS, which failed to increase plasma BBS levels, replaced phase I activity in the stomach and duodenum by intense irregular spike activity and decreased the occurrence rate of MMCs, whereas intravenous infusion of BBS evoked phase II-like activity, mainly in the jejunum and ileum, and suppressed phase III activity. These data suggest that the effect of i.c.v. administration of BBS was mediated by direct activation of central brain structures. During i.c.v. perfusion of BBS, cycling in plasma levels of motilin persisted even when phase III activity was absent and plasma levels of epinephrine rose significantly. Epinephrine infusion, however, did not affect myoelectric gastrointestinal activity except for prolonging phase II. Thus it is unlikely that the central action of BBS is exerted by motilin or epinephrine.

Clinical research on plasma motilin levels and cutaneous electrogastrogram in patients with functional dyspepsia

Clinical research on plasma motilin levels and cutaneous electrogastrogram in patients with functional dyspepsia

Role of bile acids in duodenal migrating motor complexes in dogs.

Previous studies have suggested that enterohepatic circulation of bile acids is essential for regular cycling of duodenal migrating motor complexes (MMCs). The present study was an attempt to clarify the role of bile acids in the enterohepatic circulation system in initiating duodenal MMCs. Seven dogs underwent total external biliary diversion that resulted in the loss of MMCs originating from the duodenum. Sodium ursodeoxycholate (6 mg/kg/hr) was then given either through the portal vein or a peripheral vein, and motility of the gastrointestinal tract was serially recorded. When sodium ursodeoxycholate was given either through the portal vein or a peripheral vein during external biliary diversion, duodenal MMCs restarted. The cyclic change in plasma motilin levels during an MMC cycle as induced by sodium ursodeoxycholate was almost the same as in a normal MMC cycle. Total bile acid concentration in the portal vein changed cyclically with MMC cycles when bile flow was intact but did not change cyclically with MMC cycles restarted by intravenous bile salt infusion. Bile acid stimulation of putative receptors existing between the portal vein and intrahepatic bile ducts may be involved in initiating normal duodenal MMC cycles.

Disturbed initiation of gastric interdigestive migrating complexes despite high plasma motilin levels in patients with low gastric pH.

It is known that there is a close relationshipbetween serum motilin fluctuation and the initiation ofgastric interdigestive migrating complexes (IMC) (1).The administration of synthetic motilin initiates IMC (2), and antimotilin serum blocks theinitiation of IMC (3). Erythromycin has recently beenshown to be a motilin-receptor agonist (4), and motilinreceptors have been found in the human stomach (5). At present motilin is considered to initiateIMC through both the vagal cholinergic pathway anddirect stimulation of smooth muscle. From the clinicalpoint of view, Labo et al (6) and our group (7) recently reported on the relationship between a lowmotilin concentration and disturbance of IMC in patientswith dyspepsia. On the other hand, little is known aboutthe effect of an abnormally high motilin concentration on gastroduodenal motility. We have found threeoutpatients in our clinic at Gunma University Hospitalwith duodenal ulcer or duodenitis who had disturbedinitiation of IMC despite an abnormally high plasma motilin concentration.

Rhythmic oscillating complexes in gastrointestinal tract of chickens: a role for motilin.

Rhythmic oscillating complex (ROC) is a highly organized gastrointestinal motility pattern recently described in fasted avian species. ROCs show several high-speed aborad-propagated contractions that progressively change into others of orad direction. In addition, chickens show migrating motor complexes (MMC) in both fed and fasting states. Recently, motilin was isolated and characterized from chicken small intestine. Accordingly, the aim of this study was to learn whether chicken motilin might be involved in either ROC or MMC induction. Electromyographic recordings were obtained from different areas of the gastrointestinal tract of chickens while motilin was infused. The response to chicken motilin was dose dependent in both fed and fasted animals; a bolus of 4 x 10(-11) mol/kg (n = 5) did not modify the intestinal motor pattern, whereas 4 x 10(-10) and 4 x 10(-9) mol/kg (n = 5 each) induced a complete ROC pattern of 5.2 +/- 0.6 and 10.8 +/- 0.9 min, respectively. ROCs induced by chicken motilin presented exactly the same pattern as that described during a spontaneous ROC. Furthermore, motilin concentration in plasma, measured by radioimmunoassay, increased during a spontaneous ROC. This study suggests that chicken motilin triggers an ROC in chickens. The fact that plasma motilin levels increased during spontaneous ROC strongly suggests that motilin is involved in the induction of the ROC pattern. Motilin seems to play a different role in avian and mammalian species, because a phase III of the MMC was never induced by motilin infusion.

Initiative investigation on the level of plasma motilin in diarrhea and constipation

Initiative investigation on the level of plasma motilin in diarrhea and constipation

Clinical evaluation of fasting plasma motilin levels in patients with gastric esophageal diseases

Clinical evaluation of fasting plasma motilin levels in patients with gastric esophageal diseases

Coordination of biliary and upper gastrointestinal motility in the fasted conscious pig

A chronic pig model was developed which permits the simultaneous measurement of integrated biliary motility as resistance to flow (CBD inflow), gallbladder, duodenal and gastric motility in addition to collection of venous blood samples for gut hormones estimations. Animals displayed a duodenal interdigestive cycle of 55.4 +/- 3.4 min (mean +/- SEM, n = 6), consisting of phase I, II and III (21.2 +/- 2.1, 70.5 +/- 2.0, 8.7 +/- 0.5% of the cycle, respectively). A gastric interdigestive cycle of 60.2 +/- 6.5 min (n = 4) was similarly demonstrated consisting of three phases which corresponded to the three duodenal phases. The gastric phases I, II and III comprised 26.3 +/- 3.0, 71.2 +/- 2.7 and 2.5 +/- 0.8% of the cycle, respectively. The gastric phase III immediately preceded the onset of the duodenal phase III. The gallbladder likewise displayed an interdigestive cycle of 54.5 +/- 7.2 min (n = 6) consisting of a quiescent period (37.2 +/- 3.7% of the cycle) corresponding temporally to duodenal phase III and phase I. This quiescent phase was followed by a period of rhythmic contractions (64.5 +/- 4.1% of the cycle) which corresponded temporally to duodenal phase II. The onset of the gallbladder quiescent period coincided with the onset of duodenal phase III. The CBD inflow similarly demonstrated an interdigestive cycle of 53.4 +/- 9.6 min (n = 4) duration, consisting of three phases. The initial phase was evident as a period of rapid inflow, the onset of which coincided with the onset of duodenal phase III and the gallbladder quiescent period, and occupied 12.0 +/- 0.8% of the cycle. The second phase which occupied 18.0 +/- 7.4% of the cycle, was typified as a period of declining inflow which reached a relatively stable level at a time corresponding to the end of duodenal phase I. The third phase consisted of the maintenance of the inflow rate achieved at the end of the previous phase (60% of maximum inflow), corresponding in onset and duration with duodenal phase II and occupied 70.0 +/- 8.6% of the cycle. Plasma motilin levels fluctuated in relation to the duodenal interdigestive cycle, peaking during phase III relative to phase I (36.9 +/- 8.5 vs 25.4 +/- 7.7 pg mL-1, respectively, n = 5, P < 0.05). Cholecystokinin levels did not fluctuate, remaining low (2.3 +/- 2.1 pM cholecystokinin octapeptide equivalents, n = 5) throughout the duodenal interdigestive cycle, but increased about two fold after ingestion of solid food. Feeding disrupted the gastric, duodenal, gallbladder and CBD inflow cycles.

Vagus-Dependent and Vagus-Independent Mechanisms of Action of the Erythromycin Derivative EM574 and Motilin in Dogs

The motor-stimulating action of de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) on the upper gastrointestinal tract was studied in fasted conscious dogs using chronically implanted force transducers and compared with those of porcine motilin and cisapride. EM574 induced gastric phase Ill-like migrating contractions and increased the plasma motilin levels slightly. The gastric motility induced by low doses of EM574 and motilin was abolished by a 5HT3-receptor antagonist ondansetron and acute vagal blockade, whereas under these conditions, high doses of both agents induced contractions, which were abolished by atropine. Cisapride-induced gastric motility was inhibited by atropine and acute vagal blockade, but not by ondansetron. EM574 did not stimulate gastric secretion in the basal state. These results indicate that EM574- and motilin-induced gastrointestinal motility is attributable mainly to motor-stimulating vagal cholinergic neurons, and 5HT3-receptors are probably involved in the process. At high doses, EM574 and motilin also appear to stimulate cholinergic neurons in a non-vagal pathway, probably the enteric nervous system.

Increased Plasma Levels of Pancreatic Polypeptide and Decreased Plasma Levels of Motilin in Encopretic Children

Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P < .05) for encopretic patients. The motilin response was lower (P < .03) for encopretic children than for controls. We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Prospective study of autonomic nerve function in type 1 and type 2 diabetic patients: 24 hour heart rate variation and plasma motilin levels disturbed in parasympathetic neuropathy.

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

GUT HORMONE RELEASE IN PATIENTS AFTER SPINAL CORD INJURY

Gastrointestinal disorders including abdominal pain, abdominal distention, ileus, and constipation are common after spinal cord injury. In physiologic studies of patients with spinal cord injury, slow gastric emptying, ileal dilation, and abnormal rectosigmoid motility have been found. However, it is not yet known whether abnormal gut hormone release is important in the development of these abnormalities. In healthy volunteers, there are postprandial increases in plasma peptide YY and motilin levels, which appear related to neural mechanisms. We hypothesized that abdominal sympathetic pathways provide tonic inhibition of peptide YY and motilin release and that postprandial increases in these gut hormones are mediated through spinal pathways. Fasting serum was obtained from normal volunteers, paraplegic patients, and tetraplegic patients. In studies in which patients were fed, serum was obtained from normal volunteers, paraplegic patients, and tetraplegic patients before and at 30-min intervals after a 280 kcal meal. Serum motilin and peptide YY levels were measured by radioimmunoassays. In fasting studies, there was a trend (P = 0.23) toward increased fasting serum motilin in paraplegic patients, and this result did not support tonic inhibition of motilin release. Fasting peptide YY levels were not increased in spinal cord injury patients, which did not support tonic inhibition of peptide YY release. In fed studies, there were strong trends toward postprandial increases in serum peptide YY in volunteers and paraplegic patients and a significant postprandial rise in serum peptide YY in tetraplegic patients (P = 0.04). This was evidence against involvement of spinal pathways in postprandial release of peptide YY.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythromycin enhances fasting and postprandial proximal gastric tone in humans

Background & Aims: Low doses of erythromycin induce antral contractions and accelerate gastric emptying. However, the effect of erythromycin on the proximal stomach remains unknown. The aim of this study was to assess the effect and mechanism(s) of action of erythromycin on proximal gastric tone in humans. Methods: Gastric tone was measured using an electronic barostat in two groups of 6 subjects both in the fasting state and after a 200-kcal meal. On different occasions, subjects received saline, atropine alone (6 μ · kg −1 · h −1 for 30 minutes), erythromycin alone (1.5 mg/kg in the fasting state and 1.5 and 3.0 mg/kg in the postprandial state), and erythromycin plus atropine. Results: Low-dose (1.5 mg/kg) erythromycin enhanced fasting gastric tone, but only the 3.0-mg/kg dose reduced the duration of meal-induced relaxation (37 ± 14 vs. 105 ± 20 minutes; P < 0.01). Atropine did not change the fasting or postprandial gastric tone as well as the erythromycin-induced responses. Plasma motilin levels were unaffected by erythromycin infusion. No correlation was observed between gastric tone and plasma motilin or erythromycin levels. Conclusions: Erythromycin enhances fasting and postprandial proximal gastric tone in humans by a mechanism that does not seem to involve endogenous motilin release or a cholinergic pathway.

Increased Plasma Levels of Pancreatic Polypeptide and Decreased Plasma Levels of Motilin in Encopretic Children

Objective. Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. Methods. Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. Results. Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P &amp;lt; .05) for encopretic patients. The motilin response was lower (P &amp;lt; .03) for encopretic children than for controls. Conclusions. We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Purification and amino acid sequence of human motilin isolated from a motilin containing liver metastasis

The acid extract of a liver metastasis from a patient with elevated plasma motilin levels contained large quantities of motilin (3.37 μg/ml). The extract was concentrated on a C 18-column and motilin was isolated by gel chromatography (Sephadex G-50) followed by cation ion exchange chromatography (HR5/5 Mono-S) and three successive steps of reverse phase chromatography (Nucleosil 300-5 C 18). The pure peptide was sequenced and the identity of porcine and human motilin was confirmed. This is the first report of a tumor containing large amounts of motilin.

Gastrointestinal peptide hormones during postoperative ileus. Effect of octreotide.

The hypothesis was that postoperative ileus might be caused by a disturbed balance between the motor-stimulating hormones, motilin and substance P, and the motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs with chronic gastrointestinal electrodes, electrical activity was recorded and blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then induced by celiotomy and intestinal abrasion. During and after operation, five dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P, and VIP were changed little by operation, but cyclical increases in plasma motilin, which occurred preoperatively during phase III of the interdigestive myoelectric complex, were completely abolished postoperatively during ileus, as was the complex itself. Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not do so by increasing plasma motilin or substance P or decreasing plasma VIP.

Effects of hyperglycemia on interdigestive gastrointestinal motility in humans.

Gastrointestinal motility disorders are common in patients with diabetes mellitus. Recent studies indicate that hyperglycemia can affect gastric emptying and gastric motility in healthy subjects and diabetics. The effect of acute hyperglycemia on gastrointestinal motility was studied with a manometric technique in healthy subjects. Seven individuals, four men and three women, 23-34 years old, were studied on 2 different days. On 1 of the days a 5-h registration was performed after an overnight fast. On another day and after an initial basal period, acute steady-state hyperglycemia was induced by intravenous glucose infusion for 90 min. Motility variables were evaluated in four segments: in the gastric antrum, the proximal duodenum, the distal duodenum, and the proximal jejunum. Fasting migrating motor complex rhythm including migration of phase III prevailed during hyperglycemia. Compared with euglycemia, the motility index in phase II was lower during hyperglycemia in all segments studied. In the antrum the difference was 62% (p < 0.01); in the proximal duodenum, 37% (p < 0.01); in the distal duodenum, 44% (p < 0.05); and in the jejunum, 58% (p < 0.01). During hyperglycemia the prevalence of propagated contractions in phase II was significantly lower than during euglycemia both in the antrum and the proximal duodenum. In the last part of phase III in proximal duodenum most individual contractions were propagated in orad direction compared with early phase III, and this difference persisted during hyperglycemia. The number of long clusters was significantly increased during hyperglycemia as compared with euglycemia: 2.0 +/- 0.6 per hour versus 0.4 +/- 0.14 (p < 0.01). In late phase II plasma levels of motilin and pancreatic polypeptide were significantly decreased during hyperglycemia. Hyperglycemia not only reduces the motility in the stomach but also inhibits motility in both the duodenum and the jejunum. The results show that acute hyperglycemia has an important impact on small-intestinal motility.

&lt;b&gt;BINDING OF HUMAN PLACENTAL RIBONUCLEASE INHIBITOR TO EXTRACELLULAR MATRIX &lt;/b&gt;&lt;b&gt;MOLECULES &lt;/b&gt;

For clarification of the etiology of juxtapapillary duodenal diverticula (JPD), intraduodenal pressure and fasting phasic motility, particularly in phase III (migrating motorcomplex, MMC) were recorded using a micro-tip transducer in 15 normal subjects and 5 patients with JPD. Plasma motilin and somatostatin levels were measured when phase I or III was shown. A duodenojejunostomy was performed without invading the diverticulum. The usefulness of this surgical method was assessed based on changes before and after surgery during MMC and the plasma levels of motilin and somatostatin. The following results were obtained