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1.
Rev Assoc Med Bras (1992) ; 69(2): 279-284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36888769

RESUMO

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.


Assuntos
Grelina , Motilina , Criança , Humanos , Motilina/genética , Grelina/genética , Serotonina , Constipação Intestinal/genética , Polimorfismo Genético
2.
Sci Adv ; 9(11): eade9020, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36921049

RESUMO

Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of Gq-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders.


Assuntos
Motilina , Receptores dos Hormônios Gastrointestinais , Humanos , Motilina/metabolismo , Eritromicina/farmacologia , Eritromicina/metabolismo , Receptores dos Hormônios Gastrointestinais/química , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo
3.
Zhen Ci Yan Jiu ; 48(1): 88-94, 2023 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-36734504

RESUMO

OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.


Assuntos
Terapia por Acupuntura , Diabetes Mellitus , Gastroparesia , Humanos , Gastroparesia/etiologia , Gastroparesia/terapia , Baço , Domperidona/uso terapêutico , Gastrinas , Motilina , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa , Interleucina-6 , Glicemia , Hemoglobinas Glicadas , Fígado , Superóxido Dismutase , Pontos de Acupuntura , Diabetes Mellitus/terapia
4.
Gen Comp Endocrinol ; 330: 114140, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228737

RESUMO

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 (10-10 M - 10-6 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.


Assuntos
Motilidade Gastrointestinal , Trato Gastrointestinal , Motilina , Contração Muscular , Animais , Humanos , Coelhos , Galinhas , Trato Gastrointestinal/fisiologia , Motilina/química , Salamandridae , Estômago , Peixe-Zebra
5.
Comput Math Methods Med ; 2022: 1221190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267315

RESUMO

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica , Probióticos , Humanos , Infecções por Helicobacter/tratamento farmacológico , Bismuto/farmacologia , Bismuto/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons/farmacologia , Gastrinas/farmacologia , Gastrinas/uso terapêutico , Motilina/farmacologia , Motilina/uso terapêutico , Comprimidos com Revestimento Entérico/farmacologia , Comprimidos com Revestimento Entérico/uso terapêutico , Quimioterapia Combinada , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Antibacterianos/uso terapêutico , Probióticos/uso terapêutico , Pectinas/farmacologia , Pectinas/uso terapêutico , Somatostatina/farmacologia , Somatostatina/uso terapêutico
6.
Cell Mol Biol (Noisy-le-grand) ; 68(6): 98-104, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36227672

RESUMO

it was aimed to investigate the efficacy and safety of cupping moxibustion in patients with functional diarrhea. 51 patients diagnosed with functional diarrhea from January 2021 to December 2021 were selected as the objects, and they were randomly divided into the control group (oral montmorillonite powder) and the experiment group (oral montmorillonite powder combined with cupping moxibustion). The number of diarrheas, Bristol stool, traditional Chinese medicine (TCM) syndromes, clinical efficacy indexes, self-rating anxiety scale (SAS) score, the MOS item short from health survey (SF-36) scale score, peripheral blood cell levels of CD4+, CD8+, and Th17, gastrin (GAS), motilin (MTL), and cholecystokinin (CCK) levels was assessed before and after treatment. The adverse events were also recorded. Compared with those before treatment, all indexes of both groups were significantly improved (P<0.05). Compared with those of the control group, the number of diarrheas, Bristol stool, TCM syndrome score, SAS score, and CD8+ cell levels was significantly decreased after treatment in the experiment group (P<0.05). The clinical cure rate (48.0% vs. 73.1%), SF-36 score, GAS, MTL, CCK contents, and CD4+, and Th17 cell levels were significantly increased (P<0.05). No significant difference was in the incidence of adverse events between the two groups (P>0.05). It could be suggested that cupping moxibustion could be applied in the treatment of functional diarrhea, improving the clinical symptoms, relieving anxiety, enhancing gastrointestinal and immune functions, and promoting the quality of life of patients significantly.


Assuntos
Moxibustão , Bentonita , Colecistocinina , Diarreia/terapia , Gastrinas , Humanos , Imunidade , Motilina , Pós , Qualidade de Vida
7.
Ter Arkh ; 94(2): 194-199, 2022 Feb 15.
Artigo em Russo | MEDLINE | ID: mdl-36286744

RESUMO

AIM: To establish the role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin (M-cells) in the occurrence of cholelithiasis. MATERIALS AND METHODS: The first group included 122 patients with cholelithiasis. The second group consisted of 30 healthy individuals who underwent medical examination. The groups were matched for gender and age. The work analyzed anamnestic, biochemical and anthropometric data. All patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucous membrane from the antrum. Biopsies were subjected to cytological and immunohistochemical studies in order to verify Helicobacter pylori and estimate the number of M-cells. RESULTS: Patients with cholelithiasis more often belonged to the group of people of mental labor, had low physical activity, were committed to inappropriate nutrition and more often indicated the presence of aggravated heredity for cholelithiasis. Patients with gallstone disease had higher body mass index, waist volume, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, lower high-density lipoprotein cholesterol, H. pylori infection was more often verified and M-cell hypoplasia in the mucous membrane was established. stomach in comparison with the representatives of the second group. CONCLUSION: Our results suggest that certain external factors, nutritional characteristics of the metabolic syndrome components, hypoplasia of M-cells in the gastric mucosa are important factors in the formation of calculi in the gallbladder.


Assuntos
Colelitíase , Células Endócrinas , Infecções por Helicobacter , Helicobacter pylori , Humanos , Motilina , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Estômago , Mucosa Gástrica , Colelitíase/epidemiologia , Fatores de Risco , Triglicerídeos , Células Endócrinas/patologia , Colesterol , Glucose , Lipoproteínas HDL , Lipoproteínas LDL
8.
Surg Obes Relat Dis ; 18(12): 1392-1398, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36151028

RESUMO

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD/DS) results in lifelong changes in gastrointestinal physiology with unclear associations with appetite perception. OBJECTIVE: To explore mixed meal-induced changes in glucose homeostasis and gut hormones and their correlations with appetite perception. SETTING: University hospital. METHODS: Of 28 patients studied preoperatively (age: 38.4 ± 11.3 years; body mass index [BMI]: 56.5 ± 5.1 kg/m2; 14 women), 19 (68%) returned for postoperative follow-up. Plasma was sampled for 180 minutes during a 260-kcal standardized mixed meal. Concentrations of leptin, glucose, insulin, triglycerides, active acyl-ghrelin, motilin, total glucose-dependent insulinotropic polypeptide (GIP), active glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY) were measured. Subjective appetite sensations were scored. RESULTS: BPD/DS resulted in 66.1% ± 23.3% excess BMI loss. Leptin was halved. Glucose and insulin levels were reduced, blunting a preoperative peak at 30 minutes, giving a lower homeostasis model assessment for insulin resistance (HOMA-IR; 13.9 versus 4.8). In contrast, reduced ghrelin and motilin concentrations were accompanied by pronounced peaks 20-30 minutes prior to meal responses. GIP was reduced, whereas GLP-1 and PYY responses were markedly increased, with an early postprandial peak (P < .05, for all). HOMA-IR correlated with insulin (r = .72) and GIP (r = .57). Postoperatively, satiety correlated with GLP-1 (r = .56), whereas the gastric motility index correlated with the desire to eat (r = .60), percentage excess BMI loss (r = -.55), and percentage total weight loss (r = -.49). Delta insulin, GLP-1, and leptin correlated positively with percentage total weight loss (r = .51, r = .48, and r = .58, respectively). CONCLUSIONS: BPD/DS reduces leptin, HOMA-IR, and GIP while markedly increasing GLP-1 and PYY. This study marks the magnitude change in GLP-1 with additional effects of PYY as important factors for weight loss.


Assuntos
Desvio Biliopancreático , Hormônios Gastrointestinais , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Apetite , Leptina , Motilina , Polipeptídeo Inibidor Gástrico , Peptídeo YY , Peptídeo 1 Semelhante ao Glucagon , Redução de Peso , Insulina , Homeostase , Glucose
9.
Comput Math Methods Med ; 2022: 5169892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799630

RESUMO

Functional dyspepsia (FD) is a common digestive system disease, and probiotics in the treatment of FD have a good curative effect. Patients with gastrointestinal diseases often show a poor response to traditional drug treatments and suffer from adverse reactions. Kvass can be used as a functional drink without side effects to improve the symptoms of FD patients. The results showed that compared with those of the model group, the body weight and food intake of the treatment group were significantly increased (P < 0.05), and the gastric residual rate of the treatment group was significantly decreased (P < 0.05); the amount of pepsin in the treatment group was significantly higher than that in the model group (P < 0.05); a high dose of Kvass could increase the contents of ghrelin, motilin (MTL), and gastrin (GAS) in the plasma and decrease the contents of vasoactive intestinal peptide (VIP) in the plasma; the contents of ghrelin, MTL, and GAS in the gastric antrum were also increased in the high-dose group. Kvass beverage can significantly improve the gastrointestinal function of rats, which may be because it can improve the contents of ghrelin, MTL, GAS, and VIP in both the serum and gastric antrum by regulating the expression of short-chain fatty acids in the colon.


Assuntos
Dispepsia , Animais , Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal/fisiologia , Grelina , Motilina/metabolismo , Motilina/farmacologia , Ratos , Estômago/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 812-816, 2022 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-35894198

RESUMO

OBJECTIVES: To study the effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen. METHODS: A total of 102 children with acute abdomen who underwent surgery in Xuzhou Children's Hospital from August 2019 to June 2021 were enrolled as subjects and were randomly divided into an observation group and a control group, with 51 children in each group. The children in the control group were given conventional treatment such as hemostasis and anti-infective therapy after surgery, and those in the observation group were given somatostatin in addition to conventional treatment. Peripheral blood samples were collected from both groups before surgery and on days 1 and 5 after surgery. The two groups were compared in terms of the serum levels of endothelin-1 (ET-1), adrenocorticotropic hormone (ACTH), cortisol, gastrin, and motilin, postoperative recovery, and the incidence rate of complications. RESULTS: There was no significant difference in the serum levels of ET-1, ACTH, cortisol, gastrin, and motilin between the two groups before surgery (P>0.05). Compared with the control group, the observation group had significantly lower serum levels of ET-1, ACTH, and cortisol on days 1 and 5 after surgery (P<0.05) and significantly higher levels of motilin and gastrin on day 5 after surgery (P<0.05). Compared with the control group, the observation group had significantly shorter time to first passage of flatus, first bowel sounds, and first defecation after surgery, as well as a significantly shorter length of hospital stay (P<0.05). The incidence rate of complications in the observation group was significantly lower than that in the control group (6% vs 24%, P<0.05). CONCLUSIONS: In children with acute abdomen, somatostatin can significantly reduce postoperative stress response, improve gastrointestinal function, and reduce the incidence rate of complications, thereby helping to achieve a good prognosis.


Assuntos
Abdome Agudo , Motilina , Abdome , Hormônio Adrenocorticotrópico , Criança , Gastrinas , Humanos , Hidrocortisona , Complicações Pós-Operatórias , Estudos Prospectivos , Somatostatina/uso terapêutico
11.
Turk J Gastroenterol ; 33(6): 477-484, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35786615

RESUMO

BACKGROUND: Chronic atrophic gastritis is a very common condition in the general clinical practice of gastroenterology. Tuina treatment is widely used clinically. The aim of our study was to investigate the mechanisms of tuina in rats with chronic atrophic gastritis. METHODS: Fifty-six specific pathogen-free grade rats were employed for our study. They were divided into 5 groups and treated differ- ently. Body weight was recorded every week, and their small intestine propulsive ratio was measured after intragastric administration of carbon powder. Histopathological observation of gastric tissues was performed using hematoxylin and eosin staining. The levels of motilin and gastrin in serum were detected by enzyme-linked immunosorbent assay, and the expression levels of Bcl-2 and cytochrome C were measured by the western blot assay. RESULTS: There was no significant difference in body weight and small intestine propulsive ratio between the chronic atrophic gastritis model group and the tuina group (P > .05). However, we can see some significant changes in histomorphology after treatment with tuina. For example, the atrophy of gastric mucosal epithelium and glands had improved, and the inflammatory cells infiltrating the lamina propria were decreased significantly. Moreover, the level of gastrointestinal hormone GAS was increased (P < .001), and there was no statistically significant difference in motilin, Bcl-2, and cytochrome-c after treatment with tuina (P > .05). CONCLUSION: Our research demonstrated the effectiveness of tuina treatment on chronic atrophic gastritis with a possible underlying mechanism that affected the secretion of gastric acid, which could provide some useful information for clinical application.


Assuntos
Gastrite Atrófica , Animais , Atrofia , Peso Corporal , Mucosa Gástrica , Massagem , Motilina , Ratos
12.
Biomed Res Int ; 2022: 4803956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425842

RESUMO

Objective: This study was aimed at investigating the potential mechanism of Grubthobrildkr (GTB) on systemic hypoxia-induced gastric ulcers in rats and at detecting the chemical profile of GTB. Methods: Male Sprague-Dawley rats were separated into control, hypoxia, hypoxia+omeprazole, and hypoxia+GTBs (0.25, 0.5, and 1.0 g·kg-1·d-1) groups. Systemic hypoxia was created in a hypobaric chamber to simulate 5000 m high altitude by adjusting the inner pressure and oxygen content for 6 days. After that, the ulcer index, pH, and volume of gastric juice were assessed. The levels of endothelin-1 (ET-1), gastrin (GAS), motilin (MTL), phospholipase A2 (PLA2), and prostaglandin E2 (PGE2) were detected by ELISA. The expression level of hydrogen potassium ATPase (H+-K+-ATPase), cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) was tested by western blotting. Chemical profile of GTB was revealed by UHPLC-Q-exactive hybrid quadrupole-orbitrap mass (UHPLC-Q-Orbitrap MS). Results: GTB decreased the ulcer index in rats under hypoxia for six days, which was related to increased pH and volume of gastric juice, enhanced MTL and PGE2 levels, and decreased ET-1 and PLA2 levels of gastric mucosa. Furthermore, GTB decreased the level of H+-K+-ATPase and COX-2 while increased COX-1 levels in gastric mucosal tissue. 44 constituents were identified by UHPLC-Q-Orbitrap MS in GTB. Conclusion: GTB exerted a gastroprotective effect to alleviate gastric ulceration induced by acute systemic hypoxia in rats. The effect of GTB increasing the volume and pH of gastric juice in rats under acute systemic hypoxia could be regulated by gastrointestinal hormones, including MTL and ET-1. Mechanically, gastrointestinal protection of GTB was based on inhibition of the protons pumping H+-K+-ATPase and regulation of prostaglandin family in rats.


Assuntos
Úlcera Gástrica , Adenosina Trifosfatases/metabolismo , Animais , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Mucosa Gástrica/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Masculino , Medicina Tradicional Tibetana , Motilina , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera
13.
Gen Comp Endocrinol ; 323-324: 114031, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35331740

RESUMO

Motilin, a peptide hormone consisting of 22 amino acid residues, was identified in the duodenum of pigs in the 1970s. It is known to induce gastrointestinal contractions during the interdigestive state in mammals. Although the motilin gene has been identified in various animal species, it has not been studied in amphibians. Here, we identified the motilin gene in the Japanese fire bellied newt (Cynops pyrrhogaster), and conducted an analysis of tissue distribution, morphological observations, and physiological experiments. The deduced mature newt motilin comprises 22 amino acid residues, like in mammals and birds. The C-terminus of the newt motilin showed high homology with motilin from other species compared to the N-terminus region, which is considered the bioactive site. Motilin mRNA expression in newts was abundant in the upper small intestine, with notably high motilin mRNA expression found in the pancreas. Motilin-producing cells were found in the mucosal layer of the upper small intestine and existed as two cell types: open-and closed-type cells. Motilin-producing cells in the pancreas were also found to produce insulin but not glucagon. Newt motilin stimulated gastric contractions but not in other parts of the intestines in vitro, and motilin-induced gastric contraction was significantly inhibited by treatment with atropine, a muscarinic acetylcholine receptor antagonist. These results indicate that motilin is also present in amphibians, and that its gastrointestinal contractile effects are conserved in mammals, birds, and amphibians. Additionally, we demonstrated for the first time the existence of pancreatic motilin, suggesting that newt motilin has an additional unknown physiological role.


Assuntos
Motilina , Salamandridae , Aminoácidos , Animais , Aves/metabolismo , Motilidade Gastrointestinal , Mamíferos/metabolismo , Motilina/farmacologia , Contração Muscular , RNA Mensageiro/metabolismo , Salamandridae/genética , Salamandridae/metabolismo , Suínos
14.
Pharmacol Res Perspect ; 10(2): e00900, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35191209

RESUMO

The gastrointestinal (GI) hormone motilin helps control human stomach movements during hunger and promotes hunger. Although widely present among mammals, it is generally accepted that in rodents the genes for motilin and/or its receptor have undergone pseudonymization, so exogenous motilin cannot function. However, several publications describe functions of low concentrations of motilin, usually within the GI tract and CNS of mice, rats, and guinea pigs. These animals were from institute-held stocks, simply described with stock names (e.g., "Sprague-Dawley") or were inbred strains. It is speculated that variation in source/type of animal introduces genetic variations to promote motilin-sensitive pathways. Perhaps, in some populations, motilin receptors exist, or a different functionally-active receptor has a good affinity for motilin (indicating evolutionary pressures to retain motilin functions). The ghrelin receptor has the closest sequence homology, yet in non-rodents the receptors have a poor affinity for each other's cognate ligand. In rodents, ghrelin may substitute for certain GI functions of motilin, but no good evidence suggests rodent ghrelin receptors are highly responsive to motilin. It remains unknown if motilin has functional relationships with additional bioactive molecules formed from the ghrelin and motilin genes, or if a 5-TM motilin receptor has influence in rodents (e.g., to dimerize with GPCRs and create different pharmacological profiles). Is the absence/presence of responses to motilin in rodents' characteristic for systems undergoing gene pseudonymization? What are the consequences of rodent supplier-dependent variations in motilin sensitivity (or other ligands for receptors undergoing pseudonymization) on gross physiological functions? These are important questions for understanding animal variation.


Assuntos
Trato Gastrointestinal/fisiologia , Motilina/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo , Animais , Variação Genética , Grelina/metabolismo , Cobaias , Humanos , Camundongos , Ratos , Receptores de Grelina/metabolismo , Roedores , Especificidade da Espécie
15.
Curr Opin Endocrinol Diabetes Obes ; 29(2): 191-199, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081068

RESUMO

PURPOSE OF REVIEW: In this review, we evaluate recent findings related to the association between gastrointestinal hormones and regulation of gastric emptying. RECENT FINDINGS: Motilin and ghrelin, which act during fasting, promote gastric motility, whereas most of the hormones secreted after a meal inhibit gastric motility. Serotonin has different progastric or antigastric motility effects depending on the receptor subtype. Serotonin receptor agonists have been used clinically to treat dyspepsia symptoms but other hormone receptor agonists or antagonists are still under development. Glucagon-like peptide 1 agonists, which have gastric motility and appetite-suppressing effects are used as a treatment for obesity and diabetes. SUMMARY: Gastrointestinal hormones play an important role in the regulation of gastric motility. Various drugs have been developed to treat delayed gastric emptying by targeting gastrointestinal hormones or their receptors but few have been commercialized.


Assuntos
Gastroenteropatias , Hormônios Gastrointestinais , Jejum , Esvaziamento Gástrico , Fármacos Gastrointestinais/farmacologia , Gastroenteropatias/tratamento farmacológico , Hormônios Gastrointestinais/fisiologia , Motilidade Gastrointestinal/fisiologia , Grelina , Humanos , Motilina/farmacologia , Motilina/fisiologia , Motilina/uso terapêutico
16.
Neurogastroenterol Motil ; 34(4): e14249, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34536258

RESUMO

BACKGROUND/AIMS: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. METHODS: Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. KEY RESULTS: Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). CONCLUSIONS & INFERENCES: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms.


Assuntos
Grelina , Pancreatite , Dor Abdominal , Doença Aguda , Motilidade Gastrointestinal/fisiologia , Humanos , Inflamação , Motilina , Pancreatite/complicações , Pancreatite/terapia , Fator de Necrose Tumoral alfa
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-939667

RESUMO

OBJECTIVES@#To study the effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen.@*METHODS@#A total of 102 children with acute abdomen who underwent surgery in Xuzhou Children's Hospital from August 2019 to June 2021 were enrolled as subjects and were randomly divided into an observation group and a control group, with 51 children in each group. The children in the control group were given conventional treatment such as hemostasis and anti-infective therapy after surgery, and those in the observation group were given somatostatin in addition to conventional treatment. Peripheral blood samples were collected from both groups before surgery and on days 1 and 5 after surgery. The two groups were compared in terms of the serum levels of endothelin-1 (ET-1), adrenocorticotropic hormone (ACTH), cortisol, gastrin, and motilin, postoperative recovery, and the incidence rate of complications.@*RESULTS@#There was no significant difference in the serum levels of ET-1, ACTH, cortisol, gastrin, and motilin between the two groups before surgery (P>0.05). Compared with the control group, the observation group had significantly lower serum levels of ET-1, ACTH, and cortisol on days 1 and 5 after surgery (P<0.05) and significantly higher levels of motilin and gastrin on day 5 after surgery (P<0.05). Compared with the control group, the observation group had significantly shorter time to first passage of flatus, first bowel sounds, and first defecation after surgery, as well as a significantly shorter length of hospital stay (P<0.05). The incidence rate of complications in the observation group was significantly lower than that in the control group (6% vs 24%, P<0.05).@*CONCLUSIONS@#In children with acute abdomen, somatostatin can significantly reduce postoperative stress response, improve gastrointestinal function, and reduce the incidence rate of complications, thereby helping to achieve a good prognosis.


Assuntos
Abdome , Abdome Agudo , Hormônio Adrenocorticotrópico , Criança , Gastrinas , Humanos , Hidrocortisona , Motilina , Complicações Pós-Operatórias , Estudos Prospectivos , Somatostatina/uso terapêutico
18.
Zhen Ci Yan Jiu ; 46(12): 1043-7, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34970882

RESUMO

OBJECTIVE: To observe the effect and safety of injection of vitamin B1 into Zusanli (ST36) and Hegu (LI4) in the treatment of functional dyspepsia (FD). METHODS: A total of 100 FD patients were equally divided into medication group and acupoint injection group (n=50/group) according to a random number table. Patients in the medication group were ordered to take mosapride citrate tablets (5 mg) orally 30 min before each of the three meals, while those in the acupoint injection group received injection of vitamin B1 into ST36 and LI4, once every other day, three times a week. One week later, the clinical symptom scores, total effective rates, serum gastrin (GAS) and plasma motilin (MTL) contents, and gastric emptying rates between the two groups were compared, followed by the observation of adverse reactions. Two weeks' follow-up survey was conducted after the end of treatment, and the clinical symptom scores and total effective rates of the two groups were further compared. RESULTS: Compared with the data before treatment in the same one group, the clinical symptom scores and serum GAS contents of post-treatment as well as the follow-up symptom scores were all significantly decreased (P<0.05,P<0.01), while the plasma MTL levels and gastric emptying rates were obviously increased in both groups (P<0.01). Comparison between the two groups showed that the clinical symptom score, serum GAS content after the treatment and follow-up symptom score were considerably lower (P<0.01), but the total effective rate, plasma MTL, gastric emptying rate after the treatment and total effective rate of follow-up notably higher in the acupoint injection group than those in the medication group (P<0.01,P<0.05). CONCLUSION: Injection of vitamin B1 into ST36 and LI4 is effective in improving symptoms of PD patients, which may be related to its functions in regulating the levels of GAS and MTL in blood, and facilitating gastrointestinal motility.


Assuntos
Terapia por Acupuntura , Dispepsia , Pontos de Acupuntura , Dispepsia/tratamento farmacológico , Humanos , Motilina , Tiamina
19.
Mol Metab ; 54: 101356, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34662713

RESUMO

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 Ca2+ 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.


Assuntos
Bile/metabolismo , Duodeno/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Motilina/metabolismo , Organoides/metabolismo , Células Cultivadas , Humanos , Concentração de Íons de Hidrogênio
20.
Peptides ; 143: 170574, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34082070

RESUMO

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 EC50 was 8.8 × 10-8 ± 0.9 × 10-8 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.


Assuntos
Artérias/metabolismo , Endotélio Vascular/metabolismo , Motilina/metabolismo , Receptores dos Hormônios Gastrointestinais/genética , Receptores de Neuropeptídeos/genética , Animais , Cães , Feminino , Trato Gastrointestinal/irrigação sanguínea , Regulação da Expressão Gênica , Masculino , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo
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