Isamu Aizawa

Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs

Simultaneous measurement of plasma motilin concentration and gastrointestinal contractile activity was made in 12 healthy dogs. Plasma motilin concentration was measured by radioimmunoassay and gastrointestinal contractile activity was monitored by means of chronically implanted force transducers. During the interdigestive state, it was found that the plasma motilin concentration increased in complete accordance with the cyclical interdigestive contractions of the stomach. Furthermore, plasma motilin concentration was lowered by the ingestion of food, and it remained low as long as the gastric motor activity was in the digestive pattern. Since, as reported previously, the interdigestive contractions can be induced by the exogenous administration of motilin, we concluded that (1) motilin is released at constant intervals during the interdigestive state, and this release is suppressed by the ingestion of food; (2) motilin induces the interdigestive contractions of the stomach and duodenum; and (3) motilin is an interdigestive hormone and is the only known polypeptide hormone of the gut whose release is not induced by a meal.

An extraluminal force transducer for recording contractile activity of the gastrointestinal smooth muscle in the conscious dogs: its construction and implantation.

SummaryAn extraluminal strain-gauge force transducer has been developed for recording contractile activity of the gastrointestinal smooth muscle. The details of its construction and implantation were described. The transducer unit allows for continuous long-term recordings (more the 5 months) from conscious experimental animals. It could be constructed in any laboratory and easily implanted in animals if it is done in aseptic technique. Since it is sutured onto the outside of the gut, it does not interfere passage of the contents. The only disadvantages are that it only measures muscle contractions and it is hard to determine movements of intraluminal contents especially in the digestive state.

Comparison of Gallbladder Contractions Induced by Motilin and Cholecystokinin in Dogs

Contractile activity in the gallbladder was measured by means of chronically implanted force transducers in conscious dogs. Intravenous infusion o f motilin (0.3–0.9 mg/kg·h) induced transient contractions during the interdigestive but not during the digestive period. The contractions of the gallbladder occurred simultaneously with the initiation of phase 2 contractions in the duodenum. The duration (5.9 ± 0.15 min) and the contractile force (11.5 ± 0.57 g) were not different from those with three doses o f motilin. The motilin-induced contractions, however, started with dose-related periods of latency and terminated before the cessation of motilin infusion. In contrast, cholecystokinin-octapeptide (0.03–0.09 μg/kg·h) induced dose-dependent tonic contractions (7.8 ± 0.41 g to 17.7 ± 0.77 g) not only during the interdigestive period but also during the digestive period. These contractions also started with dose-related periods of latency and lasted the duration of the infusion. Atropine sulfate (0.025 mg/kg) inhibited both motilin and cholecystokinin—octapeptide-induced contractions of the gallbladder. The present study reveals that motilin has a stimulus effect on the gallbladder only during the interdigestive period and that motilin-induced contractions were different from those induced by cholecystokinin—octapeptide, a common stimulator of the gallbladder.

Diurnal changes in gastric motor activity in conscious dogs.

Twenty-four-hour changes in gastric motor activity were recorded in 4 healthy adult dogs in the conscious state by means of extraluminal force transducers. Three major different gastric motor activity patterns were recognized during 24 hr: digestive, intermediate, and interdigestive. The digestive pattern was characterized by steady low-amplitude contractions in the gastric antrum, with no significant motor activity in the gastric body. The interdigestive pattern considted of series of high-amplitude contractions of 14–23 min duration in both the gastric body and antrum with intervening and long-lasting (68–109 min) motor quiescence. The intermediate pattern is considered to be the pattern midway when the digestive pattern is changing to the interdigestive pattern. These changes in gastric motor activity are precisely controlled day after day if the animals are fed at regular time intervals and are healthy. The digestive pattern may represent principally a mixing function of ingested food and the interdigestive pattern a cleaning function in preparation for the next meal.

Characteristic motor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers.

Gastrointestinal contractile activity from the gastric body to the terminal ileum in conscious dogs was continuously recorded for several weeks by means of chronically implanted strain-gage force transducers. It was found that the 24-hr changes in the gastrointestinal contractile activity consisted of the two different major patterns, the digestive and interdigestive patterns. In the interdigestive state, a cyclic, recurring, caudad-moving band of strong contractions starting in the stomach and the duodenum and traversing the entire length of the small intestine was observed. When one band of strong contractions reached the distal ileum, another developed in the stomach and the duodenum again and propagated in a caudad direction. Such recycling episodes interrupted by long-lasting quiescence repeatedly occurred until the next meal. These characteristic contractile activities observed in our dogs are identical with the interdigestive myoelectric complex of the stomach and the small bowel recently reported by Code and Marlett (5). Four sequential phases (I–IV) of the migrating myoelectric complex, defined in terms of action potential activity, seem to correspond to the resting (quiescence), preceding irregular contractions, strong contractions, and subsiding contractions observed in the present study, respectively. Function and control mechanism of the interdigestive contractile activity were discussed.

Interdigestive motor activity of the lower esophageal sphincter in the conscious dog

Simultaneous measurements of motor activity in the lower esophageal sphincter (LES) and the stomach were recorded continuously for several weeks by means of chronically implanted force transducers in five conscious dogs. We found that the LES contracted precisely in association with the gastric body during the interdigestive state. During this time a series of simultaneous contractions arose in the LES, gastric body, and antrum; these contractions lasted for 25±2.1 min and then stopped abruptly. This active period was followed by a long period of motor quiescence (78±3.6 min). These cyclic recurring episodes of contractions in the LES and the stomach continued until the next meal. Our findings suggest that the interdigestive contractions in the LES act as the orad seal of the stomach during the interdigestive contractions and thus prevent the reflux of the gastric contents into the esophagus during this period.

Effect of synthetic motilin on gastric motor activity in conscious dogs.

The effect of intravenous infusion of synthetic motilin on gastric motor activity was investigated by means of chronically implanted force transducers in 4 conscious dogs. Since the gastric motor pattern consisted of two major subpatterns, digestive and interdigestive motor activity, motilin was tested for its motor stimulating activity in both states. It was found that motilin had no influence upon gastric motor activity in the digestive state. However, during the interdigestive state, intravenous infusion of motilin in doses of 0.3–2.7 μg/kg/hr induced motor activity similar to the naturally occurring interdigestive contractions in a dose-related fashion. Since motilin is released by duodenal alkalinization in the dog, it may be postulated that motilin is a substance to control the interdigestive contractions in the dog, although other reports describe motilin release by duodenal acidification and inhibition of gastric emptying in man. Endogenous stimuli leading to motilin release may be different among species. The present study clearly indicates that motilin induces a contractile pattern similar to that seen during the interdigestive state in conscious dogs.

Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs

The effect of synthetic motilin on contractile activity in the lower esophageal sphincter (LES) and the stomach has been studied in 5 healthy dogs by means of chronically implanted strain gage force transducers. Motilin produced strong contractions in the LES and the stomach simultaneously after intravenous doses ranging from 0.3 to 2.7 μg/kg hr, which were similar to the naturally occurring interdigestive contractions in the LES and the stomach. However, these contractions could be induced only in the interdigestive state; infusion of motilin into dogs in the digestive state brought about no significant effect on either the LES or the stomach. Motilin-induced contractions in the LES and the stomach were instantly abolished by ingestion of food. It is considered that the contractions induced by motilin are identical with the naturally occurring interdigestive contractions in the LES and these contractions are the most orad component of the interdigestive cyclic recurring caudad-moving bands of strong contractions in the dogs.

Recent Advances in Motilin Research: Its Physiological and Clinical Significance

Since 1975, when motilin was synthesized in Japan1,2, we concentrated our efforts on various aspects of motilin in man and dog. We have found that: 1.) motilin induces the cyclic recurring episodes of caudad-moving bands of strong contractions that move from the lower esophageal sphincter (LES) to the terminal ileum, 2.) motilin has no significant influence upon the gastrointestinal contractile activity during the digestive state, and 3.) the naturally-occurring and motilin-induced gastric contractions are completely abolished by the ingestion of food or the i.v. infusion of pentagastrin3,4. These actions of motilin are all related to the interdigestive function of the gut and, therefore, we have proposed the name “interdigestive hormone” for motilin5. Recently, we have developed a RIA for motilin and this then enabled us to measure changes in plasma motilin concentration. Moreover, we synthesized fragments and an analogue of motilin, the biological activity of which was also investigated.

Inhibitory effect of pentagastrin and feeding natural and motilin-induced interdigestive contractions in the stomach of conscious dogs.

SummaryThe interaction between motilin, pentagastrin and feeding was investigated during the interdigestive gastric motor state in 4 healthy conscious dogs. We confirmed previous reports that an i.v. infusion of synthetic motilin always induced a pattern precisely like that of the naturally-occurring interdigestive contractions of the stomach. Pentagastrin inhibited the occurrence of the interdigestive contractions at dose between 0.2–1.6 μ/kg-hr; this inhibition had a dose-related relationship to the occurrence of the motilin-induced contractions. The ingestion of food strongly inhibited the occurrence of not only the natually-occurring contractions but also the motilin-induced contractions in the stomach and changed the motor pattern to the digestive one. These findings strongly support our hypothesis that the interdigestive contractions in the dog are, at least in part, under the control of motilin. Furthermore, it should be emphasized that pentagastrin not always stimulates gastric motor activity but conversely, in the interdigestive state it inhibits movements characteristic of that condition and replaces them with the digestive pattern.