Dopamine interrupts gastrointestinal fed motility pattern in humans

The aim of this study was to investigate the hypothesis that during the postprandial period in humans, dopamine interrupts the gastrointestinal motility pattern through a mechanism that is peptide-mediated. Fourteen normal human subjects were studied by means of intestinal manometry. After recording two consecutive migrating motor complexes a 900-kcal solid-liquid meal was given. In eight subjects 30 min after the meal, placebo or dopamine (5 micrograms/kg/min) was infused for 15 min and then the recording continued for 120 min. In the remaining six subjects dopamine was administered twice with a 90-min interval in between. In three subjects the first dopamine infusion after the meal was preceded by treatment with placebo, the second by domperidone (20 mg intravenous as bolus), in the other three subjects domperidone was given before the first dopamine infusion. Blood samples for the determination of somatostatin and motilin were drawn basally, during, and immediately after dopamine in seven subjects. The results show that dopamine interrupts the fed motility pattern, inhibiting the high antral waves, and activates a duodenal phase III of migrating motor complexes. The pretreatment with domperidone completely prevented the dopamine effect. Plasma levels of motilin increased significantly during dopamine, while somatostatin blood levels did not change. These findings support the hypothesis that a dopaminergic mechanism may modulate the cycling of duodenal motor complex in humans.     

Morphine and Gastroduodenal Motility

This study investigated the effects ofintravenous morphine on gastric antral and duodenalmotility in healthy volunteers. Intravenous morphine(both infusion and bolus) increased duodenal motility,typically as bursts of contractions similar to phase IIIof the migrating motor complex. Intravenous infusion ofmorphine 40 g/kg/hr rapidly increased duodenalmotility in nine of 10 subjects; in eight it was phase III-like. Intravenous infusion ofnaloxone (40 g/kg/hr) blocked this effect ofmorphine infusion in five of six subjects. Morphinebolus injection (5-20 g/kg) in six subjects (30-42min following a spontaneous phase III) induced furtherduodenal phase III-like activity; also, morphine bolusinjection (5-20 g/kg) in five subjects (30-42 minfollowing a liquid meal) induced duodenal phase III-like activity. Atropine (10 g/kg intravenously)was able to prevent the action of morphine (bothintravenous infusion and intravenous bolus injection) ininducing this phase III-like activity. Theseobservations show: (1) morphine in very low dose is able tostimulate maximal duodenal contractility; (2) themotility response is typically phase III-like; and (3)morphine acts on opioid receptors to initiate this phase III-like activity, with the effectblocked by antimuscarinic drugs.     

Milk feeding and xylazine treatment induce increased antroduodenal motility in young cattle with opposite effects on duodenal digesta flow rate

Antroduodenal myoelectrical activity and duodenal digesta flow rate in young cattle were assessed by implanted nichrome wire electrodes and reentrant duodenal cannulation with interposed flow-meter. In addition, a small glass electrode was inserted through a duodenal cannula to continuously measure the pH of duodenal contents. When eating only hay ad libitum, the duodenal myoelectrical activity showed the usual migrating myoelectrical complex (MMC) pattern. Duodenal contents pH rose sharply at the end of a period of repetitive spike activity (RSA), or phase III, from pH<2 to >5 and remained high through most of the subsequent period of no spike activity (NSA), or phase I, during which there was no antrat spiking and no flow of duodenal contents. Feeding milk (pH 6.5) caused a marked increase in antroduodenal spike activity and intraduodenal flow rate, with a concomitant rapid rise in duodenal contents pH from 1.8±0.3 (sem) to 5.0±0.2 which then slowly declined over the next few hours. Within 5 min after the administration of the ₂-adrenergic agonist xylazine (25 and 50 g/kg intramuscular), there was a significant increase (P<0.05) in antroduodenal spike frequency and a concomitant marked drop in intraduodenal flow rate with a sustained low pH of intraduodenal contents. The results suggest that: (1) continuous measurement of proximal duodenal pH adds a useful dimension to documenting relationships between antroduodenal myoelectrical activity and duodenal digesta flow rate; and (2) increased spike activity in the antroduodenal region does not necessarily indicate an increased duodenal flow rate is occurring.     

Fasting canine biliary secretion and the sphincter of Oddi

This study correlates duodenal bile acid delivery with motility of the sphincter of Oddi during the fasting state. Dogs were prepared with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes serosally implanted from stomach to terminal ileum. In one set of experiments, the bile acid pool was depleted, and during a continuous i.v. infusion of sodium taurocholate (20 mumol/min), duodenal bile acid delivery was assessed over 6 h by a marker perfusion technique. In other experiments, a double-lumen continuously perfused manometry catheter was placed to record motility in the bile duct and sphincter of Oddi for a period of 6 h. Station pull-throughs of the sphincter of Oddi were performed in each phase of the migrating motor complex. Bile acid secretion rates fluctuated about the i.v. infusion rate during duodenal phase I and II, peaked in late phase II, and then fell to barely detectable levels during duodenal phase III. There was no peristaltic contractile activity in the common bile duct in any phase of the migrating motor complex. The sphincter of Oddi maintained a baseline pressure above common bile duct pressure. It was highest during phase III. Phasic contractions of the sphincter of Oddi were intermittent during phase I, increasingly frequent during phase II, and continuous during duodenal phase III of the migrating motor complex. Contractions were frequently peristaltic. We concluded that the occurrence and amplitude of phasic peristaltic contractions of the sphincter of Oddi are cyclically coordinated with the fasting intestinal motor pattern (migrating motor complex), and with cyclical variations in the delivery of bile acids into the duodenum. Both resting pressure and phasic contractions of the sphincter appear to play a role in coordinating the cyclic delivery of bile acids into the duodenum with the migrating motor complex. Intense phasic motor activity appears to impede bile flow, and less intense activity allows or facilitates flow.     

Scintigraphic measurements of canine ileocolonic transit. Direct and indirect effects of eating

Eight dogs were equipped with ileal catheters, 50 cm proximal to the ileocolonic junction, and serosal electrodes at 5, 25, 55, 100, and 150 cm. Transit was assessed by injecting a bolus of 99mTc-diethylenetriamine pentaacetic acid through the ileal catheter and following isotope movements by serial, 4-min scintiscans. Isotope was injected in separate studies: during phase I of an interdigestive myoelectrical cycle, 10 min before a meal, and or 2 or 4 h after a meal (600 ml, 385 kcal, thickened with 4 g guar). At another time, mouth-to-colon transit of the same meal was measured by labeling it with 111In-diethylenetriamine pentaacetic acid and scanning at hourly intervals for 11 h. Transit of isotope through the terminal ileum and entry into the colon was characteristically erratic; long periods of immobility were interspersed with sudden "bolus" movements. In the fasting studies, most sudden movements occurred while phase III (migrating motor complex) of the interdigestive myoelectrical cycle migrated through the last 50 cm of ileum. Passage of a single migrating motor complex through the terminal ileum propelled about one-half the dose of isotope into the colon; complete clearance of the ileum required two or more migrating motor complexes. Immediately after the meal, ileal movements increased transiently; however, these were followed by a period of quiescence. Overall, the time for 50% of the counts to enter the colon was not different when isotope was injected 10 min before the meal from when the injection was made 2 h postprandially (207 +/- 16 min and 162 +/- 25 min, respectively). However, transit of isotope injected 4 h postprandially was significantly faster (91 +/- 13 min). In the fed state, some bolus movements could be related to specific patterns of ileal motility; however, the majority occurred during apparently random "fed-type" motility. In part II, meal marker accumulated faster in the colon after 3-4 h, suggesting that the rapid ileocecal transit at 4 h postcibal was due to increased flow of chyme through the ileum at this time.     

The influence of induced hyperglycaemia on the characteristics of intestinal motility and bile kinetics in healthy men.

Simultaneous recording of duodenal motility and biliary scintigraphy by continuous infusion of 99mTc-dimethyl-iminodiacetic acid was performed in 16 healthy fasted men, of whom eight had an intravenous glucose bolus injection immediately after the passage of a duodenal phase III of the migrating motor complex (MMC). This was followed by a continuous intravenous infusion of glucose. Characteristics of the time-activity curves from the gallbladder area and intestinal area were related to phase activity of the duodenal MMC. The median duration of the entire MMC cycle was significantly shorter in the glucose group than in the group without glucose. The difference was caused by shortening of phase II. Spontaneous gallbladder emptying appeared in all eight subjects from the group without glucose but in only a single subject from the glucose group. The relative amount of liver bile diverted to the gallbladder in the entire cycle was significantly higher in the subjects who received glucose, and in four subjects all the hepatic bile was diverted to the gallbladder. The results demonstrate that induced hyperglycaemia exerts a pronounced effect on gastrointestinal motility and bile kinetics. Available evidence suggests that the effects are caused by a 'medical vagotomy'.     

The Influence of Induced Hyperglycaemia on the Characteristics of Intestinal Motility and Bile Kinetics in Healthy Men

Simultaneous recording of duodenal motility and biliary scintigraphy by continuous infusion of ^99mTc-dimethyl-iminodiacetic acid was performed in 16 healthy fasted men, of whom eight had an intravenous glucose bolus injection immediately after the passage of a duodenal phase III of the migrating motor complex (MMC). This was followed by a continuous intravenous infusion of glucose. Characteristics of the time-activity curves from the gallbladder area and intestinal area were related to phase activity of the duodenal MMC. The median duration of the entire MMC cycle was significantly shorter in the glucose group than in the group without glucose. The difference was caused by shortening of phase II. Spontaneous gallbladder emptying appeared in all eight subjects from the group without glucose but in only a single subject from the glucose group. The relative amount of liver bile diverted to the gallbladder in the entire cycle was significantly higher in the subjects who received glucose, and in four subjects all the hepatic bile was diverted to the gallbladder. The results demonstrate that induced hyperglycaemia exerts a pronounced effect on gastrointestinal motility and bile kinetics. Available evidence suggests that the effects are caused by a ‘medical vagotomy'.     

Effects of smoking on interdigestive gastrointestinal motility

The effect of smoking on interdigestive gastrointestinal motility is little studied but may play a role in gastrointestinal morbidity. We studied gastroduodenal motility in 10 volunteers (five smokers and five nonsmokers) using a water-perfused pressure catheter. A pH probe was placed in the duodenal bulb. Baseline motility was recorded until phase III of the migrating motor complex had occurred in the stomach three times in order to record two complete cycles of MMC activity. Subjects then began smoking until phase III activity occurred again (mean duration of smoking 117 min). During the control period, all subjects had normal MMC cycles and there were no differences between smokers and nonsmokers. While smoking, no gastric phase III was observed in any subject and gastric motility was markedly reduced. In seven of 10 subjects, smoking did not prevent the occurrence of normal duodenal phase III activity. Three subjects had no duodenal phase III activity during smoking. The duodenal pH profile did not change during smoking and motilin levels continued to fluctuate in conjunction with phase III activity. In conclusion, smoking abolished phase III activity in the stomach without affecting the plasma motilin cyclic fluctuations or duodenal bulb pH. In contrast, smoking has little effect on duodenal motility.     

Effects of central and peripheral administration of dopamine on pattern of intestinal motility in dogs

The central vs peripheral effects of dopamine on the motility pattern of the small intestine were investigated by electromyography in four conscious dogs, chronically fitted with transparietal duodenal and jejunal electrodes. In the fasted dog intracerebroventricular administration of dopamine (10g/kg) increased the duration of the interval between two consecutive migrating myoelectric complexes (MMC) while the intravenous administration at a 10-fold higher dose induced in 37.5% of trials a phase of regular spiking activity propagated over the duodenum and the jejunum. When dopamine was centrally administered 1 hr before a daily meal, the duration of the postprandial disruption of the MMC pattern was significantly (P<0.01) reduced from 9.4±1.8 to 3.2±1.3 hr at the level of the duodenum. Peripheral administration of dopamine did not modify the duration of the postprandial disruption. All of the central and peripheral effects persisted after vagotomy. It is concluded that in the dog dopamine acts centrally to modify the food-induced disruption of the MMC pattern and the frequency of the interdigestive myoelectric complexes.This study was supported by INRA (Animal Pathology Department).     

Stimulation of beta-adrenoceptors with isoprenaline inhibits small intestinal activity fronts and induces a postprandial-like motility pattern in humans.

AIMS: To investigate the effects of beta-adrenoceptor stimulation, using the agonist isoprenaline and the antagonist propranolol, on migrating motor complexes in the upper intestine of 16 healthy human volunteers. METHODS: Fasting motility was monitored using a tube with water perfused side holes connected to a pneumohydraulic system. Continuous eight hour recordings were obtained from each volunteer after a 12 hour fasting period. In all experiments, saline was given as control for the first four hour period and beta-adrenergic agents for the next four hours. In separate control studies, saline was given for the whole eight hour period. RESULTS: Isoprenaline (2.5 micrograms/kg/min) reduced the number of activity fronts (phase III) of migrating motor complexes from 3 (2-4) in controls to 1 (0-2) during isoprenaline infusion (p < 0.01). Also, phase II-like activity replaced the regular motility pattern (p < 0.01). By contrast, propranolol (25 micrograms/kg/min) did not induce any significant changes in phase III compared with controls. Saline alone had no effect on motor activity. CONCLUSIONS: Isoprenaline inhibited activity fronts in the human proximal small intestine and induced a postprandial-like motility pattern, whereas propranolol did not affect motor patterns. Stimulation of beta-adrenoceptors is of importance in the control of motor activity of the human small intestine, especially under stressful conditions with high adrenergic activity.     

Studies on mechanism of retching and vomiting in dogs

In five conscious dogs prepared with a gastric cannula and platinum monopolar electrodes in the antrum, duodenum, and jejunum, the effect of dopamine or copper sulfate on the myoelectric activity was studied. During phase 1 of interdigestive myoelectric activity, retching, and/or vomiting occurred in 1.6±0.2 (mean±se) min after intravenous bolus injection of dopamine (50 g/kg) or in 8.7±1.8 min after intragastric administration of copper sulfate (2%, 50 mg). Immediately prior to the retching and/or vomiting act, a group of disordered myoelectric activities occurred, including retrogrademoving trains of spike activity starting from the jejunum and the subsequent tachyarrhythmia in the antrum. These motility changes also occurred in the two anesthetized dogs so studied. Both the retching and/or vomiting act and the abnormal myoelectric activity which were induced by dopamine and by copper sulfate were prevented by intravenous administration of a peripheral dopamine blocker, domperidone, 5 mg, in 100% and 70%, respectively. Although domperidone could not prevent the retching and/or vomiting induced by copper sulfate in three of 10 experiments, it delayed the onset of vomiting from 8.7±1.8 to 14.5±5.3 min. A possible role of peripheral dopamine receptor on the motility disorders associated with retching and/or vomiting has been suggested.This study was supported in part by The Genesee Hospital Gastrointestinal Research Fund.     

Effect of omeprazole on interdigestive gastroduodenal motility of patients with ulcer-like dyspepsia

BACKGROUND/AIMS: As omeprazole, an antisecretory drug, is largely used in the treatment of acid-related diseases, we investigated its effects on the interdigestive gastroduodenal motility of ulcer-like dyspepsia. METHODOLOGY: Gastroduodenal motility was recorded manometrically in 9 patients complaining of ulcer-like dyspepsia with normal gastric emptying at scintigraphy, without ulcerative lesions and H. pylori infection at endoscopy, and without diseases known to affect gut motility (group ULD), and in a group of 9 healthy subjects as control (group C). After a period sufficient to record two consecutive phases III of the migrating motor complex (MMC) in patients of group ULD, omeprazole 20 mg was infused intravenously 30 min after the end of the last duodenal phase III and the recording was continued to the next one. RESULTS: With respect to the control group, the group ULD showed a significantly longer MMC cycle duration, a frequent absence of gastric phases III and a shorter duration of duodenal phases III. Omeprazole administration in group ULD was followed after 18.9 +/- 8.5 min by a typical gastroduodenal phase III and, consequently, the duration of the omeprazole-related cycle was significantly shortened. These omeprazole-related phases III started from the stomach in nearly all cases and showed a significantly longer duration at the duodenal level with respect to the spontaneous ones. CONCLUSIONS: Patients with ulcer-like dyspepsia showed a decrease in frequency and duration of gastroduodenal phases III. The omeprazole intravenous administration induced the anticipated appearance of an apparently normal gastroduodenal phase III, probably by suppressing the inhibitory action of acid secretion.     

Differential effects of acute mental stress on interdigestive secretion of gastric acid,pancreatic enzymes,and gastroduodenal motility

To study the effects of acute mental stress on gastric and pancreatic secretion, 12 healthy fasting volunteers swallowed two multilumen tubes, which allowed continuous aspiration of gastric and duodenal juices and measurement of motility of the stomach and the duodenum. In each study at least three duodenal phase III complexes of the migrating motor complex were recorded. In randomized order after the first or second duodenal phase HI, mental stress was induced for 60 min by means of solving anagrams and doing mental arithmetic. Mental stress significantly increased the duration of the migrating motor complex by 60% (137.9±16.3 vs 86.1±13.0). Gastric flow rate and gastric acid output were not significantly altered. Duodenal flow rate was not changed during the stress period but significantly decreased by more than 52% in the following 30-min resting period. Duodenal concentration and output of chymotrypsin were significantly increased during the second 30-min period of acute mental stress; tchymotrypsin output was significantly reduced in the poststress period. We conclude that acute mental stress has different effects on the stomach, the pancreas, and the upper gastrointestinal motility. The mechanisms by which the central nervous activity induced by mental stress affects the motility and secretion of the upper gastrointestinal tract remain to be elucidated.     

Influence of coronavirus (transmissible gastroenteritis) infection on jejunal myoelectrical activity of the neonatal pig

Four silver-silver chloride electrodes were surgically implanted at 5-cm intervals on the jejunal serosa of 7 neonatal pigs. Daily recordings, 7 h in duration, were made from each piglet beginning 3 days after surgery. Characteristic migrating motility complexes and short, distinct (2.5-5.0 s), rapidly aboral migrating bursts of intense spike activity ("migrating action potential complexes") were seen in all preinfection recordings. Piglets were inoculated with a 1-ml oral dose of a 0.1% gut suspension from coronavirus (transmissible gastroenteritis) infected pigs. This resulted in inappetence, vomiting, and diarrhea, most marked on the second day postinfection, but which had abated by the third day. When compared to recordings from both fed and fasted noninfected (control) animals, infection significantly altered jejunal myoelectrical activity by (a) shortening the duration of the migrating motility complex on day 1 postinfection and prolonging it on day 2, (b) increasing the number of abnormal activity fronts, and (c) decreasing the number of migrating action potential complexes. Slow wave frequency and the duration of phase 3 of the migrating motility complex were unaffected. When compared to fed control animals, infected piglets also showed a slight shortening of phase 1 of the migrating motility complex on day 1 postinfection and a prolongation on days 2 and 3, as well as a shortening of phase 2 on the second and third days postinfection. Changes in myoelectrical activity were not solely due to decreases in food intake, as abnormalities persisted when food intake returned to normal on postinfection day 3, and disruption of the activity front and migrating motility complex duration were purely transmissible-gastroenteritis-virus-induced phenomena. These findings suggest that infection with transmissible gastroenteritis virus disrupts organized propulsive activity in the jejunum of the neonatal pig.     

Effect of clarithromycin on esophageal motility

As clarithromycin (CLA), an antibiotic commonly used for Helicobacter pylori eradication, stimulates gastroduodenal motility, we investigated whether it also stimulates esophageal motility. In 15 normal subjects, esophageal motility was recorded using a low-compliance manometric system with two ports in the esophageal body, one port in the lower esophageal sphincter (LES), and five ports in the antroduodenal tract to monitor the occurrence of phases I-III of the migrating motor complex. Thirty minutes after the occurrence of a duodenal phase III, we infused intravenously, randomly, and in a double-blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B), and normal saline in the remaining five subjects (group C). LES tone and post-deglutitive residual pressure, as well as the amplitude and duration of the esophageal contractions, were measured each minute and averaged over a post-infusion period of 30 min. Both group A and B showed a LES tone significantly higher than that of group C after CLA infusion, whereas the post-deglutitive residual pressure was not significantly different from that of group C. The LES tone of group B was significantly higher than that of group A. Group B, but not group A, showed a wave amplitude and duration significantly higher than that of group C. In conclusion, CLA is able to stimulate LES tone and esophageal contractions with a dose-related effect.     

A Normal Gastrointestinal Motility Excludes Chronic Intestinal Pseudoobstruction in Children

Gastrointestinal manometry has gained wide acceptance in the approach to patients with suspected enteric neuromuscular disorders. However, performing gastrointestinal manometry in these subjects without a previous exhaustive diagnostic evaluation is unjustified. Twelve children (median age: 7.0 years; range: 8 months–13 years), with clinical and x-ray features suggesting chronic intestinal pseudoobstruction, were referred to our unit for gastrointestinal manometry. The latter was performed with a perfused catheter for 5 hr in the fasting state and for 90 min after feeding. Data were compared with those recorded in eight age-matched controls. In all patients and controls, interdigestive motor complexes with propagated phases III were detected; a regular postprandial antroduodenal motor activity was also recorded. Patients and controls did not differ for fed antral and duodenal motility indexes, fed antroduodenal coordination, and length of duodenal phase III. Most of the patients showed short or prolonged bursts of nonpropagated activity in the fasting and/or fed states; in four cases fasting and/or fed sustained phasic activity was recorded. Manometric evidence of migrating motor complexes and postfeeding activity did not support the diagnosis of intestinal pseudoobstruction and suggested redirecting the diagnostic evaluation. Final diagnoses were: Munchausen syndrome-by-proxy (four cases), celiac disease (two cases), intestinal malrotation (two cases), Crohns disease (two cases), multiple food intolerance (one case), and congenital chloride-losing diarrhea (one case). It is concluded that in children with suspected chronic intestinal pseudoobstruction manometric evidence of migrating motor complexes and fed motor activity excludes an enteric neuromuscular disorder and suggests a reassessment of the diagnostic work-up. Furthermore, if gastrointestinal manometry shows migrating motor complexes and postfeeding motor activity, qualitative abnormalities of the manometric tracings do not indicate an underlying enteric neuromuscular disorder and must not be overemphasized. Patients referred for gastrointestinal manometry should previously undergo an extensive diagnostic investigation to exclude disorders mimicking chronic intestinal pseudoobstruction.     

Effects of ghrelin on feeding regulation and interdigestive migrating complex in rats

OBJECTIVE: Ghrelin is an orexigenic peptide with remarkable prokinetic effects. However, its mechanisms in regulating feeding and gastrointestinal migrating myoelectrical complex (MMC) are not fully understood. The aim of this study was to examine the effects of ghrelin on feeding regulation and duodenal motility in rats. MATERIAL AND METHODS: Feeding regulation was investigated at different times after intravenous injection of ghrelin and its receptor antagonist (D-Lys3)GHRP-6 in fasted rats. Rats were supplied with a pair of silver bipolar electrodes embedded in the duodenal serosa for electromyography. Ghrelin was injected intravenously into the rats during the fed state or fasted state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, the 5-hydroxytryptamine3 receptor antagonist ondansetron, and (D-Lys3)GHRP-6. RESULTS: Ghrelin had little effect on food intake in the first 30 min after administration, but was found to increase feeding during the subsequent hours. (D-Lys3)GHRP-6 decreased feeding and antagonized the effect of ghrelin. Ghrelin induced duodenal MMC after administration in the fed state, and shortened the duodenal MMC cycle length and the duration of phase III during fasting. The amplitude and frequency of phase III were increased without affecting the percentage of phase III in the MMC cycle. Pretreatment with atropine, L-arginine, ondansetron, and (D-Lys3)GHRP-6 inhibited the effects of ghrelin. Propranolol and phentolamine had little influence on these effects. CONCLUSIONS: Ghrelin appears to be closely related to feeding and intestinal motility. The excitatory effects of ghrelin are dependent on the cholinergic pathway, and it has a close relationship with the NOS-NO or 5-HT pathway. The ghrelin receptor is involved in its activities.     

Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects

Gallbladder volume and interdigestive gastric and duodenal motor activity were evaluated simultaneously in 12 normal subjects. After overnight fasting, gallbladder volume was monitored every 4 min in each subject by means of real-time ultrasonography, and gastroduodenal motor activity was measured by means of a probe consisting of three polyvinyl catheters with one side opening for each catheter, placed 15 cm apart and constantly perfused with deionized water. Real-time ultrasonography and intestinal manometry were performed by different investigators and continued until at least two consecutive spontaneous phase III activities of migrating motor complexes were observed. The results show a cyclic variation of gallbladder volume, which reached its minimum value before the end of phase II in the proximal duodenum and its maximum in early phase II, 25 min after the beginning of phase III. These results suggest that there is a relationship between the cyclic gallbladder volume changes, which occur during fasting in humans, and with the various phases of duodenal migrating motor complex.     

Motilin regulation of canine interdigestive intestinal motility

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted,in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304±37 pg/ml) than during phase I (235±37 pg/ml) or phase II (235±39 pg/ml;P<0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 g/kg/min for 5 hr), begun 15–30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147±14 min before infusions to 44±3 min during the infusions (P<0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.Supported in part by USPHS NIH grants AM18278 and AM7198 and the Mayo FoundationAn abstract of this work was presented before the American Gastroenterological Association in May 1981, and published (Gastroenterology 80:1271, 1981).     

Effect of domperidone on the release of insulin after intravenous glucose load in man

To determine whether the blockade of the dopaminergic system is capable of modifying glucose-induced insulin release in man, the responses of insulin to an iv glucose load were measured at various domperidone infusion rates. The infusion of 5 micrograms/kg/min of domperidone increased significantly plasma insulin levels during the acute phase of glucose-induced insulin release and lowered plasma glucose values at 50 and 60 min; the k of glucose disappearance improved significantly. At lower domperidone infusion rates the acute increment of insulin after glucose load was indistinguishable from the response observed at 5 micrograms/kg/min until 0.5 microgram/kg/min, while similar responses in control and experimental tests were observed at 0.25 microgram/kg/min. A group of subjects was submitted to an arginine load in order to establish whether the effect observed with domperidone was specific for the glucose-induced insulin release; but, this time, we did not observe any significant effect during the domperidone-induced dopaminergic blockade. Furthermore, we also measured the plasma prolactin levels, to see whether the specific and well known effect of domperidone on prolactin release matches with the effect on beta-cell function. As far as prolactin is concerned, we observed a dose response effect of domperidone infusion, with a detectable elevation of prolactin at infusion rate of 0.25 microgram/kg/min. Since domperidone is a specific antagonist of dopamine D2-receptors, we propose that dopamine might exert a specific inhibiting effect on glucose-induced insulin release through this class of dopamine receptors.