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International Journal of Medical... 2022Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI)...
Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract. The present study investigated the effects of grape seed powder (GSP) on ICC properties and GI motility. GSP depolarized the pacemaker potentials of ICCs in a dose‑dependent manner. Y25130 or SB269970 slightly inhibited GSP‑induced effects. However, Y25130 and SB269970 together completely blocked GSP-induced effects. In the presence of inhibitors of protein kinase C, protein kinase A, or mitogen-activated protein kinase, GSP‑induced ICC depolarization was inhibited. GSP increased the intestinal transit rate in normal mice and in mice with acetic acid-induced GI motility disorder. In addition, the levels of motilin and substance P were elevated after GSP dosing. These results demonstrate that GSP can regulate GI motility, and therefore, it is a potential therapeutic agent for treating GI motility disorders.
Topics: Animals; Gastrointestinal Motility; Intestine, Small; Membrane Potentials; Mice; Patch-Clamp Techniques; Powders; Seeds; Vitis
PubMed: 35693751
DOI: 10.7150/ijms.72529 -
Revista Da Associacao Medica Brasileira... 2023Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors...
OBJECTIVE
Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria.
METHODS
Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR.
RESULTS
There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale.
CONCLUSION
Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.
Topics: Child; Humans; Motilin; Ghrelin; Serotonin; Constipation; Polymorphism, Genetic
PubMed: 36888769
DOI: 10.1590/1806-9282.20220986 -
Digestive Diseases (Basel, Switzerland) 2006Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes... (Review)
Review
Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes with prokinetic properties include antidopaminergic agents, serotonergic agents, and motilin-receptor agonists. Due to moderate prokinetic effects, poor symptomatic responses and the presence of adverse effects, there is a clear need for new classes of prokinetics. Several newer prokinetic drugs and drug classes are currently under evaluation. Selecting candidate agents and designing the appropriate therapeutic trials is hampered by the lack of insight in the pathophysiology of motility-related symptoms. As gastrointestinal motor disorders are chronic, relapsing, and remitting disorders, it seems desirable that studies with candidate prokinetic drugs establish a long-term efficacy and not only short-term effects on gastrointestinal functions.
Topics: Dopamine Antagonists; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Serotonin Antagonists; Treatment Outcome
PubMed: 16849857
DOI: 10.1159/000092883 -
Frontiers in Neuroscience 2023To observe the effects of intrathecal administration of motilin on pain behavior and expression of motilin (MTL)/motilin receptor (MTLR) in the spinal cord of a rat...
AIMS
To observe the effects of intrathecal administration of motilin on pain behavior and expression of motilin (MTL)/motilin receptor (MTLR) in the spinal cord of a rat model of acute incisional pain.
METHODS
An incisional pain model was established in rats using a unilateral plantar incision. The rats were also injected intrathecally with 1, 5, or 25 μg of motilin. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were determined. MTL/MTLR expression in the spinal cord was detected by western blotting and immunofluorescence. The expression of MTL in the spinal cord, stomach, duodenum, and plasma was determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS
Motilin/motilin receptor were detected in the spinal cord. Spinal cord MTL/MTLR expression peaks at 2 h after modeling ( < 0.05) and start to decrease at 24 h ( < 0.05) to almost reach baseline levels at 72 h. The changes in gastric, duodenal, plasma, and spinal cord motilin levels correlated with MWT and TWL (all > 0.82). The intrathecal injection of 1, 5, or 25 μg of motilin could increase the pain threshold of rats with incisional pain within 72 h in a dose-dependent manner.
CONCLUSION
This study showed for the first time that MTL/MTLR are expressed in rats' spinal dorsal horn. Acute pain increased MTL/MTLR expression in the spinal dorsal horn. Also, for the first time, this study showed that motilin intrathecal injection alleviates pain in rat models of acute incisional pain. These results suggest that MTL/MTLR could be a novel target for the management of acute pain.
PubMed: 36816129
DOI: 10.3389/fnins.2023.1104862 -
Frontiers in Physiology 2021Motilin increases left gastric artery (LGA) blood flow in dogs the endothelial motilin receptor (MLNR). This article investigates the signaling pathways of endothelial...
Motilin increases left gastric artery (LGA) blood flow in dogs the endothelial motilin receptor (MLNR). This article investigates the signaling pathways of endothelial MLNR. Motilin-induced relaxation of LGA rings was assessed using wire myography. Nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) levels were measured using an NO assay kit and cGMP ELISA kit, respectively. Motilin concentration-dependently (EC=9.1±1.2×10M) relaxed LGA rings precontracted with U46619 (thromboxane A receptor agonist). GM-109 (MLNR antagonist) significantly inhibited motilin-induced LGA relaxation and the production of NO and cGMP. N-ethylmaleimide (NEM; G-protein antagonist), U73122 [phospholipase C (PLC) inhibitor], and 2-aminoethyl diphenylborinate [2-APB; inositol trisphosphate (IP) blocker] partially or completely blocked vasorelaxation. In contrast, chelerythrine [protein kinase C (PKC) inhibitor] and H89 [protein kinase A (PKA) inhibitor] had no such effect. Low-calcium or calcium-free Krebs solutions also reduced vasorelaxation. N-nitro-L-arginine methyl ester [L-NAME; nitric oxide synthase (NOS) inhibitor] and ODQ [soluble guanylyl cyclase (sGC) inhibitor] completely abolished vasodilation and synthesis of NO and cGMP. Indomethacin (cyclooxygenase inhibitor), 18α-glycyrrhetinic acid [18α-GA; myoendothelial gap junction (MEGJ) inhibitor], and K channel inhibition through high K concentrations or tetraethylammonium (TEA-Cl; K channel blocker) partially decreased vasorelaxation, whereas glibenclamide (K channel blocker) had no such effect. The current study suggests that motilin-induced LGA relaxation is dependent on endothelial MLNR through the G protein-PLC-IP pathway and Ca influx. The NOS-NO-sGC-cGMP pathway, prostacyclin, MEGJ, and K channels (especially K) are involved in endothelial-dependent relaxation of vascular smooth muscle (VSM) cells.
PubMed: 34777026
DOI: 10.3389/fphys.2021.770430 -
Frontiers in Pharmacology 2021Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (HS) receive a bad connotation; in low concentrations these play a major governing... (Review)
Review
Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (HS) receive a bad connotation; in low concentrations these play a major governing role in local and systemic blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and HS on gut peptide release and functioning, and whether manipulation by gasotransmitter substrates or specific blockers leads to physiological alterations.
PubMed: 34354597
DOI: 10.3389/fphar.2021.720703 -
International Journal of Molecular... Mar 2019Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear....
Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear. We prepared human transgenic (Tg) mice and performed experiments evaluating the effects of motilin, erythromycin (EM), and ghrelin. EM and ghrelin promoted gastric emptying (GE) when administered either peripherally or centrally to Tg mice. Atropine (a muscarinic receptor antagonist) counteracted GE induced by centrally administered EM, but not that induced by peripherally administered EM. The administration of EM in this model promoted the effect of mosapride (a selective serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist), and improved loperamide (a μ-opioid receptor agonist)-induced gastroparesis. The level of acyl-ghrelin was significantly attenuated by EM administration. Thus, we have established an animal model appropriate for the evaluation of motilin receptor agonists. These data and the model are expected to facilitate the identification of novel compounds with clinical potential for relieving symptoms of dyspepsia and gastroparesis.
Topics: Animals; Benzamides; Erythromycin; Gastric Emptying; Gastroparesis; Ghrelin; Humans; Loperamide; Male; Mice, Inbred C57BL; Mice, Transgenic; Morpholines; Postprandial Period; RNA, Messenger; Receptors, Gastrointestinal Hormone; Receptors, Ghrelin; Receptors, Neuropeptide; Stomach; Vagus Nerve
PubMed: 30934667
DOI: 10.3390/ijms20071521 -
Journal of Smooth Muscle Research =... 2013Migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal (GI) contractions in the interdigestive state. The physiological importance of... (Review)
Review
Migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal (GI) contractions in the interdigestive state. The physiological importance of gastric MMC is a mechanical and chemical cleansing of the empty stomach in preparation for the next meal. MMC cycle is mediated via the interaction between motilin and 5-hydroxytryptamine (5-HT) by the positive feedback mechanism in conscious dogs. Luminal administration of 5-HT initiates duodenal phase II and phase III with a concomitant increase of plasma motilin release. Duodenal 5-HT concentration is increased during gastric phase II and phase III. Intravenous infusion of motilin increases luminal 5-HT content and induces phase III. 5-HT4 antagonists significantly inhibit both of gastric and intestinal phase III, while 5-HT3 antagonists inhibit only gastric phase III. These suggest that gastric MMC is regulated via vagus, 5-HT3/4 receptors and motilin, while intestinal MMC is regulated via intrinsic primary afferent neurons (IPAN) and 5-HT4 receptors. We propose the possibility that maximally released motilin by a positive feedback depletes 5-HT granules in the duodenal EC cells, resulting in no more contractions. Stress is highly associated with the pathogenesis of functional dyspepsia (FD). Acoustic stress attenuates gastric phase III without affecting intestinal phase III in conscious dogs, via reduced vagal activity. Subset of FD patients shows reduced vagal activity and impaired gastric phase III. The impaired gastric MMC may aggravate dyspeptic symptoms following a food ingestion. Maintaining MMC cycle in the interdigestive state is an important factor to prevent the postprandial dyspeptic symptoms.
Topics: Animals; Digestion; Dogs; Duodenum; Dyspepsia; Feedback, Physiological; Gastric Emptying; Humans; Intestines; Motilin; Myoelectric Complex, Migrating; Neurons, Afferent; Postprandial Period; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Stomach; Vagus Nerve
PubMed: 24662475
DOI: 10.1540/jsmr.49.99 -
World Journal of Gastroenterology Sep 2023Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA)... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available.
AIM
To explore the effect and mechanism of HPA inhibition in S-AGI patients.
METHODS
In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1, 3 and 7 d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI.
RESULTS
Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group ( < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased ( < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased ( < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups ( > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.
CONCLUSION
HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.
Topics: Humans; Gastrins; Interleukin-6; Motilin; Tumor Necrosis Factor-alpha; Sepsis; Lactic Acid; Abdominal Injuries; Fatty Acid-Binding Proteins; Heparin, Low-Molecular-Weight
PubMed: 37744293
DOI: 10.3748/wjg.v29.i35.5154 -
British Journal of Pharmacology Dec 2013A meeting of the British Pharmacological Society in association with the European Neuropeptide Club and Americal Summer Neuropeptide Conference in June 2012 led to this...
UNLABELLED
A meeting of the British Pharmacological Society in association with the European Neuropeptide Club and Americal Summer Neuropeptide Conference in June 2012 led to this themed issue on neuropetides. A wide range of neuropeptides are discussed, in various physiological and pathophysiological conditions, with respect to their upstream and downstream pathways. It is clear, at this point in time, that targeting neuropeptides has therapeutic potential in pathologies ranging from migraine to obesity. It is also clear from the reviews in this issue of the British Journal of Pharmacology that there is still so much to learn.
LINKED ARTICLES
This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.
Topics: Animals; Central Nervous System Agents; Humans; Neurons; Neuropeptides; Neurotransmitter Agents; Signal Transduction
PubMed: 24236898
DOI: 10.1111/bph.12474