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The American Journal of Gastroenterology Apr 1993Erythromycin, a commonly used antibiotic, has recently emerged as a potential gastrointestinal prokinetic agent. This follows a decade of research into the mechanism of... (Review)
Review
Erythromycin, a commonly used antibiotic, has recently emerged as a potential gastrointestinal prokinetic agent. This follows a decade of research into the mechanism of well-recognized gastrointestinal side effects of erythromycin. Early investigations demonstrated that erythromycin increased gastrointestinal motility, and more recent studies suggest that it fortuitously binds to and stimulates the receptor for the gastrointestinal peptide motilin. From this work it appears that a new and powerful class of gastrointestinal prokinetic agents will evolve from erythromycin and its derivatives. The role of motilin in the genesis of the fasting and fed patterns of gastrointestinal motility is emerging through the study of these motilin agonists.
Topics: Animals; Erythromycin; Gastric Emptying; Gastrointestinal Motility; Humans; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 8470625
DOI: No ID Found -
Clinical Pharmacy Nov 1992
Review
Topics: Diabetic Neuropathies; Erythromycin; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Motilin
PubMed: 1464218
DOI: No ID Found -
Biochemical and Biophysical Research... Jul 2015Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study,...
Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in suncus.
Topics: Animals; Atropine; Carbachol; Dose-Response Relationship, Drug; Female; Ghrelin; Injections, Intravenous; Male; Motilin; Muscarinic Antagonists; Pepsinogen A; Shrews; Vagotomy
PubMed: 25957475
DOI: 10.1016/j.bbrc.2015.04.129 -
Nihon Rinsho. Japanese Journal of... 1978
Review
Topics: Animals; Dogs; Gastrointestinal Hormones; Gastrointestinal Motility; Motilin
PubMed: 344935
DOI: No ID Found -
The American Journal of Digestive... May 1977
Review
Topics: Animals; Blood Pressure; Digestion; Dogs; Duodenum; Gastric Mucosa; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Motilin; Muscle, Smooth; Protein Biosynthesis; Stomach
PubMed: 324268
DOI: 10.1007/BF01071895 -
Minerva Pediatrics Oct 2021Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal...
BACKGROUND
Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children.
METHODS
In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms.
RESULTS
Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups.
CONCLUSIONS
This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.
Topics: Child; Child, Preschool; Constipation; Gastrointestinal Motility; Humans; Motilin; Polymorphism, Genetic
PubMed: 27706119
DOI: 10.23736/S2724-5276.16.04369-X -
General and Comparative Endocrinology Jan 2023The effects of newt motilin on the contractility of the isolated gastrointestinal (GI) tract from Japanese fire belly newts (newt) were examined to clarify whether...
Motilin is a regulator of gastric contraction in Japanese fire belly newts (Cynops pyrrhogaster), in vitro studies using isolated gastrointestinal strips of newts, rabbits, and chickens.
The effects of newt motilin on the contractility of the isolated gastrointestinal (GI) tract from Japanese fire belly newts (newt) were examined to clarify whether motilin regulates GI motility in urodele amphibians. In addition, contractile responsiveness to motilins from seven species of vertebrates (human, chicken, turtle, alligator, axolotol, newt and zebrafish) were compared in GI preparations from three different animals (rabbit duodenum, chicken ileum and newt stomach) to determine the species-specific action of motilin. Newt motilin (10 M - 10 M) caused a contraction of cognate gastric strips, while the upper, middle, and lower intestinal strips were insensitive. The rank order of motilins for contractile activity in newt gastric strips was newt > alligator > axolotol > chicken > turtle > human ≫ zebrafish. On the other hand, newt motilin caused a weak contraction in the rabbit duodenum (human > alligator = chicken > turtle > newt ≧ axolotol > zebrafish), and it was ineffective in the chicken ileum (chicken > turtle > alligator > human ≫ newt, axolotol and zebrafish). This study demonstrates that motilin induces contraction in the GI tract of a urodele amphibian, the newt, in a region (stomach)-specific manner and further indicates that a ligand-receptor interaction of the motilin system is a species-specific manner probably due to differences in the amino acid sequence of motilin.
Topics: Animals; Humans; Rabbits; Chickens; Gastrointestinal Motility; Gastrointestinal Tract; Motilin; Muscle Contraction; Salamandridae; Stomach; Zebrafish
PubMed: 36228737
DOI: 10.1016/j.ygcen.2022.114140 -
Gut Feb 2016Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor...
RATIONALE
Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin.
OBJECTIVES
To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite.
FINDINGS
In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower.
CONCLUSIONS
Motilin-induced gastric phase III is a hunger signal from GIT in man.
Topics: Appetite; Cholinesterase Inhibitors; Duodenum; Eating; Erythromycin; Gastrointestinal Motility; Ghrelin; Humans; Hunger; Manometry; Motilin; Muscle Contraction; Myoelectric Complex, Migrating; Neostigmine; Octreotide; Peptide Fragments; Somatostatin; Stomach
PubMed: 25539673
DOI: 10.1136/gutjnl-2014-308472 -
Molecular Metabolism Dec 2021Motilin is a proximal small intestinal hormone with roles in gastrointestinal motility, gallbladder emptying, and hunger initiation. In vivo motilin release is...
OBJECTIVE
Motilin is a proximal small intestinal hormone with roles in gastrointestinal motility, gallbladder emptying, and hunger initiation. In vivo motilin release is stimulated by fats, bile, and duodenal acidification but the underlying molecular mechanisms of motilin secretion remain poorly understood. This study aimed to establish the key signaling pathways involved in the regulation of secretion from human motilin-expressing M-cells.
METHODS
Human duodenal organoids were CRISPR-Cas9 modified to express the fluorescent protein Venus or the Ca sensor GCaMP7s under control of the endogenous motilin promoter. This enabled the identification and purification of M-cells for bulk RNA sequencing, peptidomics, calcium imaging, and electrophysiology. Motilin secretion from 2D organoid-derived cultures was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in parallel with other gut hormones.
RESULTS
Human duodenal M-cells synthesize active forms of motilin and acyl-ghrelin in organoid culture, and also co-express cholecystokinin (CCK). Activation of the bile acid receptor GPBAR1 stimulated a 3.4-fold increase in motilin secretion and increased action potential firing. Agonists of the long-chain fatty acid receptor FFA1 and monoacylglycerol receptor GPR119 stimulated secretion by 2.4-fold and 1.5-fold, respectively. Acidification (pH 5.0) was a potent stimulus of M-cell calcium elevation and electrical activity, an effect attributable to acid-sensing ion channels, and a modest inducer of motilin release.
CONCLUSIONS
This study presents the first in-depth transcriptomic and functional characterization of human duodenal motilin-expressing cells. We identify several receptors important for the postprandial and interdigestive regulation of motilin release.
Topics: Bile; Cells, Cultured; Duodenum; Fatty Acids, Nonesterified; Humans; Hydrogen-Ion Concentration; Motilin; Organoids
PubMed: 34662713
DOI: 10.1016/j.molmet.2021.101356 -
PloS One 2015Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect...
Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.
Topics: Animals; Anti-Ulcer Agents; Biological Transport; Famotidine; Female; Gastric Acid; Gastric Mucosa; Gastrointestinal Motility; Ghrelin; Male; Models, Animal; Motilin; Shrews; Stomach; Up-Regulation
PubMed: 26115342
DOI: 10.1371/journal.pone.0131554