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Quarterly Journal of Experimental... Oct 1984Associations between migrating myoelectric complexes (m.m.c.s) and peak plasma motilin concentrations were confirmed in the dog fasted 18 h and shown not to be present... (Comparative Study)
Comparative Study
Associations between migrating myoelectric complexes (m.m.c.s) and peak plasma motilin concentrations were confirmed in the dog fasted 18 h and shown not to be present in pigs fasted 3-4 h. Infusions of both natural porcine and synthetic 13-Nle-motilin failed to induce m.m.c.s in the pig. It was confirmed that motilin infusions stimulated the premature appearance of m.m.c.s in the dog whether motilin remained within, or exceeded, its normal plasma values. Immunoneutralization by intravenous administration of rabbit antimotilin serum was without effect on naturally occurring m.m.c.s in the dog and the pig. In the dog, antimotilin serum blocked production of m.m.c.s by exogenous motilin for 7-10 d post-immunoneutralization. It is suggested that there are both: (i) species differences in associations of m.m.c.s and plasma motilin concentration, and (ii) an independence of m.m.c.s from plasma motilin even in the dog in which normally exogenous motilin can produce m.m.c.s.
Topics: Animals; Dogs; Electrophysiology; Female; Gastrointestinal Hormones; Immune Sera; Intestines; Male; Motilin; Muscle Contraction; Muscle, Smooth; Rabbits; Species Specificity; Swine
PubMed: 6514999
DOI: 10.1113/expphysiol.1984.sp002875 -
Journal of Physiology and Pharmacology... Apr 2011Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the... (Review)
Review
Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver.
Topics: Animals; Biological Clocks; Circadian Rhythm; Gastrointestinal Hormones; Gastrointestinal Tract; Humans; Melatonin; Suprachiasmatic Nucleus
PubMed: 21673361
DOI: No ID Found -
British Journal of Pharmacology Jan 2013Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age,... (Review)
Review
Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance.
Topics: Aged; Animals; Disease Models, Animal; Electric Stimulation; Female; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; In Vitro Techniques; Individuality; Intestine, Small; Male; Models, Biological; Motilin; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Neurons; Neuropharmacology; Peristalsis; Receptors, Serotonin; Research Design; Species Specificity; Synaptic Transmission; Translational Research, Biomedical
PubMed: 22946540
DOI: 10.1111/j.1476-5381.2012.02198.x -
Molecules and Cells Jun 2019Interstitial cells of Cajal (ICCs) are pacemaker cells that exhibit periodic spontaneous depolarization in the gastrointestinal (GI) tract and generate pacemaker...
Interstitial cells of Cajal (ICCs) are pacemaker cells that exhibit periodic spontaneous depolarization in the gastrointestinal (GI) tract and generate pacemaker potentials. In this study, we investigated the effects of ghrelin and motilin on the pacemaker potentials of ICCs isolated from the mouse small intestine. Using the whole-cell patch-clamp configuration, we demonstrated that ghrelin depolarized pacemaker potentials of cultured ICCs in a dose-dependent manner. The ghrelin receptor antagonist [D-Lys] GHRP-6 completely inhibited this ghrelin-induced depolarization. Intracellular guanosine 5'-diphosphate-β-S and pre-treatment with Cafree solution or thapsigargin also blocked the ghrelin-induced depolarization. To investigate the involvement of inositol triphosphate (IP), Rho kinase, and protein kinase C (PKC) in ghrelin-mediated pacemaker potential depolarization of ICCs, we used the IP3 receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C, the Rho kinase inhibitor Y-27632, and the PKC inhibitors staurosporine, Go6976, and rottlerin. All inhibitors except rottlerin blocked the ghrelin-induced pacemaker potential depolarization of ICCs. In addition, motilin depolarized the pacemaker potentials of ICCs in a similar dose-dependent manner as ghrelin, and this was also completely inhibited by [D-Lys] GHRP-6. These results suggest that ghrelin induced the pacemaker potential depolarization through the ghrelin receptor in a G protein-, IP-, Rho kinase-, and PKC-dependent manner via intracellular and extracellular Ca regulation. In addition, motilin was able to depolarize the pacemaker potentials of ICCs through the ghrelin receptor. Therefore, ghrelin and its receptor may modulate GI motility by acting on ICCs in the murine small intestine.
Topics: Acetophenones; Amides; Animals; Benzopyrans; Boron Compounds; Calcium; Carbazoles; Gastrointestinal Motility; Ghrelin; Inositol 1,4,5-Trisphosphate Receptors; Interstitial Cells of Cajal; Intestine, Small; Macrocyclic Compounds; Membrane Potentials; Mice; Mice, Inbred ICR; Motilin; Oligopeptides; Oxazoles; Protein Kinase C; Pyridines; Receptors, Ghrelin; Signal Transduction; Staurosporine; Thapsigargin; rho-Associated Kinases
PubMed: 31250620
DOI: 10.14348/molcells.2019.0028 -
Journal of Physiology and Pharmacology... Sep 2003The stimulation of exocrine pancreatic secretion that has been attributed by Pavlov exclusively to various reflexes (nervism), was then found that it depend also on... (Review)
Review
The stimulation of exocrine pancreatic secretion that has been attributed by Pavlov exclusively to various reflexes (nervism), was then found that it depend also on numerous enterohormones, especially cholecystokinin (CCK) and secretin, released by duodeno-jejunal mucosa and originally believed to act via an endocrine pathway. Recently, CCK and other enterohormones were found to stimulate the pancreas by excitation of sensory nerves and triggering vago-vagal and entero-pancreatic reflexes. Numerous neurotransmitters and neuropeptides released by enteric nervous system (ENS) of gut and pancreas have been also implicated in the regulation of exocrine pancreas. This article was designed to review the contribution of vagal nerves and entero-hormones, especially CCK and other enterohormones, involved in the control of appetitive behavior such as leptin and ghrelin and pancreatic polypeptide family (peptide YY and neuropeptide Y). Basal secretion shows periodic fluctuations with peals controlled by ENS and by motilin and Ach. Plasma ghrelin, that is considered as hunger hormone, increases under basal conditions, while plasma leptin falls to the lowest level. Postprandial pancreatic secretion, classically divided into cephalic, gastric and intestinal phases, involves predominantly CCK, which under physiological conditions acts almost entirely by activation of vago-vagal reflexes to stimulate the exocrine pancreas, being accompanied by the fall in plasma ghrelin and increase of plasma leptin, reflecting feeding behavior. We conclude that the major role in postprandial pancreatic secretion is played by vagus and gastrin in cephalic and gastric phases and by vagus in conjunction with CCK and secretin in intestinal phase. PP, PYY somatostatin, leptin and ghrelin that affect food intake appear to participate in the feedback control of postprandial pancreatic secretion via hypothalamic centers.
Topics: Appetite Regulation; Brain; Digestive System Physiological Phenomena; Humans; Models, Biological; Pancreas
PubMed: 14566070
DOI: No ID Found -
International Journal of Physiology,... 2023To explore the effect of Shenqi millet porridge on treating gastrointestinal function decline.
OBJECTIVE
To explore the effect of Shenqi millet porridge on treating gastrointestinal function decline.
METHODS
Clinical data of 72 patients with gastrointestinal function decline were retrospectively analyzed. Patients were divided into an observation group (n=36, treated with Shenqi millet porridge) and a control group (n=36, treated with Changweikang granule) according to the treatment methods. The therapeutic effect, quality of life, nutritional status, and levels of motilin and gastrin were analyzed.
RESULTS
The total response rate of the observation group was significantly higher than that of the control group (97.22% vs. 72.22%; P<0.05). Compared with the control group, the quality of life in the observation group was increased after treatment (all P<0.05), and the total protein and body mass index in the observation group were higher than those in the control group (all P<0.05), while the levels of motilin and gastrin in the observation group were lower than those in the control group (all P<0.05).
CONCLUSION
For patients with gastrointestinal function decline, the therapeutic regimen Shenqi millet porridge ameliorates the nutritional status of patients, as well as the quality of life and total therapeutic efficacy, also reduces the levels of motilin and gastrin. This regimen has high safety and clinical application value.
PubMed: 37216173
DOI: No ID Found -
World Journal of Gastroenterology Mar 2011To investigate the effect of Simotang (Decoction of Four Powered Drugs) on gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice.
AIM
To investigate the effect of Simotang (Decoction of Four Powered Drugs) on gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice.
METHODS
Forty mice were randomly divided into control group, stress group (model group), mosapride group and Simotang group, 10 in each group. A variety of unpredictable stimulations were used to induce chronic stress in mice. Then, the mice were treated with distilled water, mosapride or Simotang for 7 d. Gastric emptying and intestinal propulsion function were detected. Serum level of motilin was measured by enzyme-linked immunosorbent assay. Expression of cholecystokinin (CCK) in intestine, spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction, respectively.
RESULTS
Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice. Furthermore, the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine, spinal cord and brain of Simotang group than in those of model group (P < 0.05). No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.
CONCLUSION
Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.
Topics: Animals; Benzamides; Brain; Cholecystokinin; Disease Models, Animal; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Gastrointestinal Agents; Gastrointestinal Motility; Immunohistochemistry; Intestine, Small; Male; Mice; Mice, Inbred ICR; Morpholines; Motilin; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord; Stress, Psychological
PubMed: 21472126
DOI: 10.3748/wjg.v17.i12.1594 -
Clinical and Translational... Apr 2022Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal...
INTRODUCTION
Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain.
METHODS
To ascertain the genetic risk factors for gastroparesis, we conducted the largest thus far whole-genome sequencing study of gastroparesis. We investigated the frequency and effect of rare loss-of-function variants in patients with both idiopathic and diabetic gastroparesis enrolled in a clinical study of gastroparesis.
RESULTS
Among rare loss-of-function variants, we reported an increased frequency of a frameshift mutation p.Leu202ArgfsTer105, within the motilin receptor gene, variant rs562138828 (odds ratio 4.9). We currently replicated this finding in an independent large cohort of gastroparesis samples obtained from patients participating in the ongoing phase III gastroparesis clinical study.
DISCUSSION
Motilin receptor is an important therapeutic target for the treatment of hypomotility disorders. The identified genetic variants may be important risk factors for disease as well as may inform treatments, especially those targeting motilin receptor.
Topics: Gastroparesis; Humans; Nausea; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Vomiting
PubMed: 35297797
DOI: 10.14309/ctg.0000000000000474 -
Alternative Therapies in Health and... Nov 2022The frequency of gastric-cancer (GC) diagnosis has been increasing in recent years and often has no obvious symptoms at an early stage. Upon clinical diagnosis of early...
CONTEXT
The frequency of gastric-cancer (GC) diagnosis has been increasing in recent years and often has no obvious symptoms at an early stage. Upon clinical diagnosis of early GC (EGC), surgical treatment is generally recommended but as an invasive operation, surgical resection can't avoid postoperative gastrointestinal dysfunction (GID) and other problems.
OBJECTIVE
The study intended to evaluate the clinical benefits for EGC patients of auricular point-pressing with beans, combined with esomeprazole magnesium (EM), for relieving gastrointestinal dysfunction (GID) after endoscopic submucosal dissection (ESD), aiming to provide accurate and effective reference opinions for future clinical treatment.
DESIGN
The research team designed a retrospective analysis.
SETTING
The study took place at the Jiangsu Province Hospital of Chinese Medicine in Nanjing, Jiangsu, China.
PARTICIPANTS
Participants were 78 EGC patients who underwent ESD at the hospital between January 2019 and January 2021 and who had developed postoperative GID.
INTERVENTION
Thirty-seven patients chose to receive routine EM treatment, and they served as a control group. 41 patients chose to receive auricular point-pressing with bean plus EM intervention, and they served as a intervention group.
OUTCOME MEASURES
At baseline and postintervention, the research team measured the levels of serum motilin (MOT), substance P (SP), prealbumin (PAB), transferrin (TF), and albumin (ALB). They also recorded the time of intestinal peristalsis recovery, first exhaust, first defecation, normal food intake, and resolution of abdominal distension symptoms. Finally, they counted the incidence of adverse events during treatment.
RESULTS
The levels of MOT, SP, PAB, TF, and ALB significantly changed between baseline and postintervention in both groups (P < .05). In the intervention group as compared to the control group postintervention, the decreases in the levels of MOT PAB, TF, and ALB and the increase in the SP level were significantly greater in the control group than those of the intervention group (all P < .05). In addition, the intervention group showed a shorter recovery time related to postoperative intestinal function and normal food intake and resolution of abdominal distension symptoms than did the control group (all P < .05), with a lower incidence of adverse events.
CONCLUSIONS
Auricular point-pressing with beans plus EM can effectively alleviate the GID of EGC patients after ESD and help them to maintain normal gastrointestinal function, and its use is worth popularizing in clinical settings.
Topics: Humans; Retrospective Studies; Esomeprazole; Endoscopic Mucosal Resection; Stomach Neoplasms; China; Treatment Outcome
PubMed: 35839117
DOI: No ID Found -
Evidence-based Complementary and... 2017To compare the effects of Semen Arecae (SA) and Charred Semen Arecae (CSA) on gastrointestinal motility, motilin, substance P (SP), and cholecystokinin (CCK) in...
AIMS
To compare the effects of Semen Arecae (SA) and Charred Semen Arecae (CSA) on gastrointestinal motility, motilin, substance P (SP), and cholecystokinin (CCK) in chronically stressed rats.
METHODS
Rats were randomly divided into control group and stress group. Rats in stress group were randomly exposed to a variety of unpredictable stimulations for 21 days. Then, the rats were treated orally with distilled water, SA, CSA, and mosapride for 7 days. Gastric residue rate and intestinal propulsion rate were evaluated. Serum levels of motilin and SP were measured by enzyme-linked immunosorbent assay (ELISA). CCK mRNA was quantified by using quantitative real-time PCR (qRT-PCR).
RESULTS
Both SA and CSA improved the intestinal propulsion and reduced the gastric residue in chronically stressed rats. Furthermore, the serum levels of motilin and SP were significantly higher and the CCK mRNA expressions in intestine and hypothalamus were downregulated in SA and CSA groups. Furthermore, it was found that CSA is more effective.
CONCLUSION
Both SA and CSA enhanced gastrointestinal motility and increased serum levels of motilin and SP in chronically stressed rats via downregulating CCK mRNA expressions in intestine and hypothalamus. Importantly, CSA possessed more effective promoting effects.
PubMed: 29375638
DOI: 10.1155/2017/1273561