Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT₃ receptors

Abstract

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats

“…Plasma motilin shows a cyclic fluctuation during the interdigestive state and its peak is highly associated with gastric phase III contractions [36]. Motilin infusion elicits gastric phase III contractions in dogs [36] and humans [37]. Although motilin has a structural resemblance to ghrelin (both peptides share eight amino acids; 27% of ghrelin and 36% of motilin), motilin does not cause any gastric contractions in rats [38].…”

Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder

“…In humans, duodenal motilin receptors are probably mainly smooth muscle receptors, while the antrum probably contains both smooth muscle and neural receptor subtypes 9–12 . Motilin has also been demonstrated as stimulating agent for gallbladder emptying in the fasted state, 13 preceding an antral phase III 14 . Finally, motilin as well as erythromycin have dose‐dependent inhibitory effects on the rabbit pylorus in vitro , because of the presence of motilin receptors on pyloric muscles as well as on inhibitory neurones innervating pyloric muscle 15 .…”

“…We hypothesized that a refractory period for antral stimulation by motilin is related to the origin of phase III that precedes infusion, partly based on observations of a prolonged MMC cycle after a normal antral phase III 3 . A refractory period for motilin‐induced gallbladder emptying may be absent, as we previously observed that antral and gallbladder emptying may be regulated by different mechanisms 14 . This implies that two subsequent motilin infusions probably will not initiate two subsequent antral phase IIIs, while gallbladder emptying may occur with each motilin infusion.…”

Effect of NO Synthesis Blocker on Electrical Activity of Rat Stomach and Small Intestine in the Early Postoperation Period

“…NO can play a role in the generation and modulation of inhibitory transmission [8]. These data suggest that NO is involved in the regulation of gastric MMC under normal conditions, but has little role in the postoperation inhibition of motor activity.…”