-
General and Comparative Endocrinology Jan 2021Ghrelin (GHRL) and motilin (MLN), gut peptides isolated from the mucosa of the stomach and duodenum, respectively, stimulate gastrointestinal (GI) motility in mammals...
Ghrelin (GHRL) and motilin (MLN), gut peptides isolated from the mucosa of the stomach and duodenum, respectively, stimulate gastrointestinal (GI) motility in mammals and birds. However, the functions of MLN and GHRL in amphibian GI tracts have not been examined in detail. To clarify the regulation of GI motility by the two peptides, the effects of human MLN and rat GHRL on contractility of isolated GI strips from three species of frogs, the black-spotted pond frog (pond frog; Pelophylax nigromaculata), bullfrog (Lithobates catesbeiana) and Western clawed frog (Xenopus; Xenopus tropicalis), were examined in in vitro experiments. The GI tract of each frog was divided into the stomach, upper intestine, middle intestine and lower intestine. Human MLN caused contractions of the stomach in the pond frog and upper intestine in the bullfrog and Xenopus, but other GI regions were insensitive to human MLN. Erythromycin did not cause contraction of the upper intestine of the bullfrog and Xenopus. Rat GHRL did not cause contraction of the stomach and small intestines in the pond frog and bullfrog, but it caused a concentration-dependent contraction in the stomach and upper intestine of Xenopus, while des-acyl rat GHRL did not cause any contraction of them. In conclusion, human MLN caused the contraction of the stomach or upper intestine in the three species of frogs, but GHRL was effective only in the stomach and upper intestine of Xenopus. On the basis of these data, MLN but not GHRL causes the GI region-dependent contractions in the frogs.
Topics: Animals; Anura; Gastrointestinal Motility; Gastrointestinal Tract; Ghrelin; Humans; In Vitro Techniques; Male; Motilin; Muscle Contraction; Rana catesbeiana; Rats; Xenopus
PubMed: 33153968
DOI: 10.1016/j.ygcen.2020.113649 -
Acta Gastro-enterologica Belgica 1995The upper gastrointestinal tract displays two different functional states: the interdigestive or fasting state, and the fed state. The fasting state is characterized by... (Review)
Review
The upper gastrointestinal tract displays two different functional states: the interdigestive or fasting state, and the fed state. The fasting state is characterized by a cyclical motor pattern, the migrating motor complex (MMC). The control of the MMC is incompletely understood. Plasma levels of the hormone motilin fluctuate in synchrony with MMC, but it is still controversial whether a motilin peak triggers the MMC or whether the MMC causes motilin release. We used the motilin agonistic properties of erythromycin to resolve this issue in man. Administration of a low dose of erythromycin induced a MMC which started from the gastric antrum, unaccompanied by a motilin peak. This finding argues against a release of motilin secondary to the MMC and supports our hypothesis that in man motilin peaks trigger the MMC. We observed that higher doses of erythromycin no longer induced a MMC, but stimulated antral contractility. The enteric nervous system is involved in the control of both the fasting and fed state at each level of the gastrointestinal tract. We hypothesized that the target for motilin to trigger the MMC is the enteric nervous system in the gastric antrum. Yet, no physiological data on antral enteric neurons were available. We performed the first electrophysiological study of myenteric neurons of the gastric antrum, revealing unique electrical and synaptic properties in comparison to other regions of the gastrointestinal tract. We confirmed the role of the enteric nervous system of the gastric antrum in the control of the MMC by directly demonstrating the presence of motilin receptors on a subpopulation of neurons. We demonstrated that endogenous and exogenous substances that stimulate (cholecystokinin, cisapride, erythromycin) or inhibit (norepinephrine, 5-hydroxytryptamine) gastric emptying all act on antral enteric neurons. These observations strongly support the hypothesis that the enteric nervous system in the gastric antrum plays a key role in the coordination of antral peristalsis and the regulation of gastric emptying. Finally, we hypothesized that the actions of erythromycin on motilin receptors on enteric neurons and intestinal smooth muscle offer a potential for therapeutic applications in gastrointestinal motility disorders. We confirmed this by demonstrating gastrointestinal motility stimulating activity of erythromycin in patients with diabetic gastroparesis.
Topics: Animals; Digestion; Eating; Enteric Nervous System; Gastrointestinal Motility; Humans; Motilin
PubMed: 7604665
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Jul 2010
Topics: Constipation; Diabetes Mellitus; Diarrhea; Humans; Inflammatory Bowel Diseases; Motilin; Radioimmunoassay
PubMed: 20960828
DOI: No ID Found -
Peptides Sep 2021Motilin's role in the regulation of vascular tone and hemodynamic besides gastrointestinal motility is concerned. This study aimed to investigate the expression of...
Differential expression of motilin receptors on the endothelium of dog gastrointestinal arteries and motilin-induced motilin receptor dependent relaxation of corresponding arteries.
BACKGROUND
Motilin's role in the regulation of vascular tone and hemodynamic besides gastrointestinal motility is concerned. This study aimed to investigate the expression of motilin receptors in gastrointestinal arteries and motilin-induced relaxation.
MATERIAL AND METHODS
The expression of motilin receptors in the left gastric artery (LGA), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) of adult dogs (1.5-5 years old) were analyzed by immunochemistry, RT-PCR, and western blotting. Motilin's effects on the gastrointestinal arteries were evaluated in a multi-wire myograph system.
RESULTS
Immunohistochemical staining showed that motilin receptor was expressed on the membranes of endothelial cells with the fluorescence intensity LGA > SMA > IMA (P < 0.01). The motilin receptor's mRNA and protein expression levels shared the same distribution patterns as it in fluorescence intensity (P < 0.01). In isolated LGA preparations precontracted with U46619 (a thromboxaneA2 analog), motilin induced a concentration-dependent relaxation, and the EC was 8.8 × 10 ± 0.9 × 10 M. Motilin-induced relaxation on the three arteries also shared the same pattern as it in fluorescence intensity (P < 0.01) and inhibited by denuded-endothelium and GM-109 (a motilin receptor antagonist) but not by atropine (a muscarinic receptor antagonist).
CONCLUSIONS
Motilin receptors are expressed differentially on the membranes of endothelial cells in dog gastrointestinal arteries with a significantly high expression in the LGA. Motilin-induced relaxation is endothelium- and motilin receptor-dependent. The motilin receptor expressed on the endothelial cell membrane of the LGA is the molecular basis for motilin regulating gastric blood flow under physiological conditions in dogs.
Topics: Animals; Arteries; Dogs; Endothelium, Vascular; Female; Gastrointestinal Tract; Gene Expression Regulation; Male; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 34082070
DOI: 10.1016/j.peptides.2021.170574 -
American Journal of Physiology.... Nov 2011Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues....
Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding effects on insulin/glucose homeostasis or adipocyte function. Our aim was to evaluate the effects of motilin on adipocyte proliferation, differentiation, lipolysis, and macronutrient uptake in adipocytes. 3T3-L1 cells and primary rat adipocytes were treated acutely and chronically with varying motilin concentrations, and effects were compared with vehicle alone (control), set as 100% for all assays. In preadipocytes, motilin stimulated proliferation ([(3)H]thymidine incorporation) and mitochondrial activity (141 ± 10%, P < 0.001 and 158 ± 10%, respectively, P < 0.001), in a concentration-dependent manner. Chronic supplementation with motilin during differentiation further increased lipogenesis (Oil red O staining 191 ± 27%, P < 0.05) and was associated with an upregulation of PPARγ (148 ± 8%, P < 0.01), C/EBPα (142 ± 17%, P < 0.05), and Cav3 (166 ± 20%, P < 0.05) expression. In mature 3T3-L1 adipocytes motilin increased fatty acid uptake/incorporation (≤ 202 ± 12%; P < 0.01) and glucose uptake (146 ± 9% P < 0.05) and decreased net fatty acid release (maximal -31%, P < 0.05) without influencing total lipolysis (glycerol release). Similar effects were obtained in primary rat adipocytes. Motilin acutely increased expression of PPARγ, CEBPβ, DGAT1, and CD36 while decreasing adiponectin mRNA and secretion. In human adipose tissue, motilin receptor GPR38 correlated with HOMA-IR and GHSR1 (r = 0.876, P < 0.0001). Motilin binding and fatty acid incorporation into adipocytes were inhibited by antagonists MB10 and [D-lys3]-GRP6 and PI 3-kinase inhibitor wortmannin. Taken together, these results suggest that motilin may directly influence adipocyte functions by stimulating energy storage.
Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Energy Metabolism; Gene Expression; Humans; Lipid Metabolism; Male; Mice; Motilin; Rats; Rats, Sprague-Dawley
PubMed: 21771971
DOI: 10.1152/ajpendo.00089.2011 -
Biomolecules Apr 2024Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression...
Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon ( ()) motilin receptor () were cloned and characterized. The results of tissue expression showed that by contrast with mammals, mRNA was richly expressed in the brain, whereas was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of to commercial feed significantly promoted the expression of in the brain during the period from day 1 to day 10, and after re-feeding with the change in expression of was partially reversed. Similarly, it was revealed that fasting increased the expression of in the brain (3 h, 6 h) and duodenum (3 h), and the expression of in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of and appetite factors expression in the brain (, , , and ) and stomach (). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in . This study lays a strong foundation for the application of as a biomarker in the estimation of hunger in juvenile during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.
Topics: Animals; Brain; Feeding Behavior; Fish Proteins; Fishes; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 38672450
DOI: 10.3390/biom14040433 -
Peptides 1998The effect of motilin on food intake was investigated in nonfood-deprived mice. A significant increase in food intake was observed 1 h after ICV administration of...
The effect of motilin on food intake was investigated in nonfood-deprived mice. A significant increase in food intake was observed 1 h after ICV administration of motilin (3 nmol/mouse) and continued for 2 h. This effect was attenuated markedly by the motilin receptor antagonist GM-109 (0.3-3 nmol/mouse) in a dose-related manner. GM-109 alone had no effect on food intake. These results indicate that motilin receptors are present in the brain and may have a role in the regulation of food intake.
Topics: Animals; Energy Intake; Hormone Antagonists; Injections, Intraventricular; Male; Mice; Motilin; Peptides, Cyclic; Swine
PubMed: 9700745
DOI: 10.1016/s0196-9781(97)00477-4 -
General and Comparative Endocrinology Jun 2013Although putative motilin receptor sequences have been reported in teleost, there is no proof for the existence of the motilin gene in teleost. In this study, we have...
Although putative motilin receptor sequences have been reported in teleost, there is no proof for the existence of the motilin gene in teleost. In this study, we have identified a motilin-like gene in the genome of several fish species and cloned its cDNA sequence from zebrafish. The zebrafish motilin-like precursor shares very low amino acid (aa) identities with the previously reported motilin precursors. Processing of the zebrafish motilin-like precursor may generate a 17-aa C-terminal amidated mature peptide, the motilin-like peptide (motilin-LP). A putative zebrafish motilin receptor (MLNR) was also identified in zebrafish. In cultured eukaryotic cells transfected with the zebrafish MLNR, zebrafish motilin-LP could enhance both CRE-driven and SRE-driven promoter activities. Tissue distribution studies indicated that the zebrafish motilin-like gene is mainly expressed in the intestine and liver while the zebrafish MLNR gene is highly expressed in brain regions, suggesting that motilin-LP behaves like other gut hormones to regulate brain functions. These data suggest that the presence of a unique motilin/MNLR system in teleost.
Topics: Animals; Fishes; Motilin; Peptides; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Zebrafish
PubMed: 23500008
DOI: 10.1016/j.ygcen.2013.02.018 -
Nihon Rinsho. Japanese Journal of... 1982
Topics: Diarrhea; Esophagus; Gastric Emptying; Gastrointestinal Hormones; Humans; Motilin
PubMed: 7120661
DOI: No ID Found -
Sheng Li Ke Xue Jin Zhan [Progress in... Apr 1983
Topics: Animals; Digestive System Physiological Phenomena; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; In Vitro Techniques; Motilin; Muscle, Smooth
PubMed: 6612299
DOI: No ID Found