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Frontiers in Endocrinology 2021Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of... (Review)
Review
Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of interdigestive migrating motor complex (MMC) in the stomach of humans, dogs and house musk shrews through the specific motilin receptor (MLN-R). Motilin-induced MMC contributes to the maintenance of normal GI functions and transmits a hunger signal from the stomach to the brain. Motilin has been identified in various mammals, but the physiological roles of motilin in regulating GI motility in these mammals are well not understood due to inconsistencies between studies conducted on different species using a range of experimental conditions. Motilin orthologs have been identified in non-mammalian vertebrates, and the sequence of avian motilin is relatively close to that of mammals, but reptile, amphibian and fish motilins show distinctive different sequences. The MLN-R has also been identified in mammals and non-mammalian vertebrates, and can be divided into two main groups: mammal/bird/reptile/amphibian clade and fish clade. Almost 50 years have passed since discovery of motilin, here we reviewed the structure, distribution, receptor and the GI motility regulatory function of motilin in vertebrates from fish to mammals.
Topics: Animals; Gastrointestinal Motility; Humans; Motilin; Muscle Contraction; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 34497583
DOI: 10.3389/fendo.2021.700884 -
Life Sciences Aug 1984Motilin isolated in 1971 from the porcine gastrointestinal tract and localized there to endocrine cells, now appears to have a CNS neural origin by RIA and... (Review)
Review
Motilin isolated in 1971 from the porcine gastrointestinal tract and localized there to endocrine cells, now appears to have a CNS neural origin by RIA and immunohistochemistry. In most species motilin releases neurotransmitters in the CNS to both increase and decrease neural transmission and in the gastrointestinal tract to increase motor activity. In the fasting animal, motilin initiates premature activity fronts of the migrating motor complex (MMC) in the upper gastrointestinal tract by an atropine or tetrodotoxin-sensitive mechanism. Immunoreactive motilin-release from the gut can be correlated with the passage of these fronts through the upper gut. In the dog, the associated events of this MMC, i.e. motor activity of the duodenum extrinsic and intrinsic neural activity and emptying of biliary and pancreatic secretions into the duodenum, all appear to contribute to the peaks in peripheral plasma immunoreactive motilin concentrations. In man, there appears to be a close association of motilin secretion with biliary and pancreatic secretions being emptied into the duodenum and less evidence for motor activity releasing motilin. Only in the dog is there strong evidence for an absolute requirement of motilin for the consolidation of the motor activity of the upper gut into the MMC. In man, the evidence is less convincing although motilin may facilitate the process and in the pig, motilin appears to have little or no role in MMC generation. No pathological consequences of hypermotilemia have been described although elevated motilin levels have been found to be associated with some diarrheal states, renal failure, and in the first week following abdominal surgery. Motilin thus remains a hormone seeking a physiological function in some species and a pathological role in all species.
Topics: Animals; Central Nervous System; Digestive System Physiological Phenomena; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Intestine, Small; Motilin; Neurons
PubMed: 6381948
DOI: 10.1016/0024-3205(84)90337-0 -
Peptides 1997Motilin is a regulatory polypeptide of 22 amino acid residues and orginates in motilin cells scattered in the duodenal epithelium of most mammals and chickens. Motilin... (Review)
Review
Motilin is a regulatory polypeptide of 22 amino acid residues and orginates in motilin cells scattered in the duodenal epithelium of most mammals and chickens. Motilin is released into the general circulation at about 100-min intervals during the interdigestive state and is the most important factor in controlling the interdigestive migrating contractions. Recent studies have revealed that motilin stimulates endogenous release of the endocrine pancreas. Clinical application of motilin as a prokinetic has become possible since erythromycin and its derivatives were proved to be nonpeptide motilin agonists.
Topics: Amino Acid Sequence; Animals; Erythromycin; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Molecular Sequence Data; Motilin; Sequence Homology, Amino Acid; Structure-Activity Relationship
PubMed: 9210180
DOI: 10.1016/s0196-9781(96)00333-6 -
Current Pharmaceutical Design 2012Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide family, share 36% amino acid sequence identity, while the human ghrelin receptor... (Review)
Review
Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide family, share 36% amino acid sequence identity, while the human ghrelin receptor exhibits a remarkable 50% overall identity with the human motilin receptor. In addition to their structural resemblance, ghrelin and motilin are the only two mammalian hormones known to decrease in the postprandial period. Ghrelin and motilin participate in initiating the migrating motor complex in the stomach, and stimulate gastrointestinal motility, accelerate gastric emptying, and induce "gastric hunger". In addition to modulating the release of growth hormone and gut motility, ghrelin plays a crucial role in the secretion and protection of the stomach and colon. Ghrelin mimetics and motilin agonists are currently being developed to reverse gastrointestinal hypomotility disorders. With additional appetite-enhancing, adiposity-promoting, and anti-inflammatory effects, ghrelin and rikkunshito (a traditional Japanese herb enhancing acyl ghrelin signaling) are superior to motilin in the treatment of cancer-related anorexia and cachexia, post-chemotherapy symptoms, rheumatological diseases, age-related frailty, as well as post-operative, septic, and post-burn gut ileus.
Topics: Animals; Drugs, Chinese Herbal; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Tract; Ghrelin; Humans; Japan; Medicine, Traditional; Motilin; Organ Specificity
PubMed: 22632857
DOI: 10.2174/138161212803216915 -
Nihon Rinsho. Japanese Journal of... Aug 2005
Review
Topics: Biomarkers; Constipation; Diabetes Mellitus; Diagnostic Techniques, Endocrine; Diarrhea; Duodenal Ulcer; Gastrointestinal Motility; Humans; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Motilin; Radioimmunoassay; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Reference Values; Specimen Handling
PubMed: 16149566
DOI: No ID Found -
Clinics in Gastroenterology Sep 1980
Comparative Study Review
Topics: Action Potentials; Animals; Digestion; Digestive System Physiological Phenomena; Dogs; Eating; Fasting; Gastric Emptying; Gastrointestinal Hormones; Gastrointestinal Motility; Guinea Pigs; Humans; Motilin; Muscle, Smooth; Rabbits
PubMed: 7000397
DOI: No ID Found -
Verhandelingen - Koninklijke Academie... 2001In order to get more insight into the mechanism of action of the gastrointestinal peptide, motilin, and its role in human physiology, we aimed at characterizing motilin... (Review)
Review
In order to get more insight into the mechanism of action of the gastrointestinal peptide, motilin, and its role in human physiology, we aimed at characterizing motilin and motilin receptors. Motilin. Sequence analysis of the motilin precursor from several species indicated that the N- and C-terminal regions of the motilin precursor have evolved at different rates. Sequence analysis of the motilin precursor in brain tissue of rabbit and man and motilin radioimmunoassay on tissue extracts, proved that motilin is a brain-gut peptide. Plasma motilin levels are increased in patients with ulcerative colitis or Crohn's disease. A weak correlation between the motilin genotype and the susceptibility to inflammatory bowel disease was demonstrated. Motilin receptors. Motilin receptors are expressed early postnatally and can be regulated by changes in its plasma level. The pharmacophore of motilin consists of the aromatic rings from Phe1 and Tyr7 and the aliphatic side chains from Val2 and Ile4. In vivo and in vitro studies showed that in the rabbit and human antrum, smooth muscle and neuronal motilin receptors exist which have different characteristics. In the rabbit duodenum motilin's action depends upon the influx of extra- and intracellular Ca2+. Nevertheless, in primary smooth muscle cultures, Ca2+ influx through L-type Ca2+ channels is the major transduction mechanism. The existence of central motilin receptors was demonstrated by autoradiography. Receptor binding studies allowed the identification of two binding sites. In contrast to antral smooth muscle cells, the response to motilin in the human TE671 medulloblastoma cell line, expressing the motilin receptor, relies on intracellular IP3-sensitive Ca2+ stores. The antibiotic erythromycin-A (EM-A) binds to the motilin receptor and induces contractions with the same regional and species specificity as motilin. This interaction was supported by the discovery of motilin antagonists. Structure activity studies led to the development of more powerful erythromycin derivatives, which lack antibiotic properties and which are now in clinical trial for treatment of hypomotility disorders. Conclusion and perspectives. The physiological role of motilin and its receptors in the brain requires further investigation. Erythromycin and its derivatives act as motilin agonists with clinically useful prokinetic potential. The motilin receptor has recently been cloned and has substantial structural homology with the growth hormone secretagogue receptor. This may not only lead to the further characterization of motilin receptor subtypes and aid the development of safe and selective motilin receptor agonists and antagonists, useful for the treatment of GI disorders, but may also give a new dimension to the role of motilin in human physiology.
Topics: Animals; Brain; Digestive System; Disease Susceptibility; Erythromycin; Gastrointestinal Agents; Humans; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 11813507
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Mar 1995
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Nihon Rinsho. Japanese Journal of... Dec 1999
Review
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Motilin
PubMed: 10778135
DOI: No ID Found -
General and Comparative Endocrinology Dec 2021Previously, pheasant motilin was identified as a 22-amino acid peptide with a sequence of FVPFFTQSDI QKMQEKERIK GQ. In the present study, the distribution of pheasant...
Previously, pheasant motilin was identified as a 22-amino acid peptide with a sequence of FVPFFTQSDI QKMQEKERIK GQ. In the present study, the distribution of pheasant motilin mRNA was determined and compared with that of ghrelin, a motilin-related peptide. The effects of pheasant motilin on the cognate gastrointestinal (GI) muscle strips were also examined in an in vitro contraction study. The expression of pheasant motilin mRNA was highest in the small intestine (duodenum, jejunum and ileum), moderate in the colon and very low in the brain, lung, heart, pancreas, esophagus, proventriculus, gizzard and caecum, and this distribution was in contrast with that of ghrelin mRNA. Pheasant motilin caused contraction of the cognate GI tract in a region-dependent manner, similar to chicken motilin. The contraction in the small intestine was large and was not affected by atropine. In contrast, contraction in the proventriculus was small and was decreased by atropine. The crop and colon were insensitive to pheasant motilin. Neither GM109 nor MA2029, mammalian motilin receptor antagonists inhibited the contractions of pheasant motilin. Erythromycin was ineffective in the pheasant ileum, although it caused contraction of the rabbit duodenum. These results indicate that pheasant motilin caused contraction through an action on smooth muscles in the small intestine and an action on enteric cholinergic nerves in the proventriculus. This high responsiveness of the small intestine suggests that motilin is a regulator of small intestinal motility in avians, and the characteristic of the motilin receptor in the pheasant might be different from that in mammals, as is that in chickens.
Topics: Animals; Chickens; Gastrointestinal Motility; Gastrointestinal Tract; Motilin; Muscle Contraction; Rabbits
PubMed: 34506789
DOI: 10.1016/j.ygcen.2021.113897