scholarly journals Motilin Comparative Study: Structure, Distribution, Receptors, and Gastrointestinal Motility

2021 ◽  
Vol 12 ◽  
Author(s):  
Takio Kitazawa ◽  
Hiroyuki Kaiya
Keyword(s):  
Endocrine Cells ◽  
Phase Iii ◽  
Regulatory Function ◽  
Experimental Conditions ◽  
Important Regulator ◽  
Hunger Signal ◽  
Interdigestive Migrating Motor Complex ◽  
Motilin Receptor ◽  
The Brain ◽  
Gi Motility

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.

scholarly journals Motilin receptor in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Anthony P. Davenport ◽  
Takio Kitazawa ◽  
Gareth Sanger
Keyword(s):  
Endocrine Cells ◽  
Species Differences ◽  
Duodenal Mucosa ◽  
Phase Iii ◽  
Macrolide Antibiotics ◽  
Large Mammals ◽  
Cholinergic Activity ◽  
Amino Acid Peptide ◽  
High Doses ◽  
Motilin Receptor

Motilin receptors (provisional nomenclature) are activated by motilin, a 22 amino-acid peptide derived from a precursor (MLN, P12872), which may also generate a motilin-associated peptide. There are significant species differences in the structure of motilin and its receptor. In humans and large mammals such as dog, activation of these receptors by motilin released from endocrine cells in the duodenal mucosa during fasting, induces propulsive phase III movements. This activity is associated with promoting hunger in humans. Drugs and other non-peptide compounds which activate the motilin receptor may generate a more long-lasting ability to increase cholinergic activity within the upper gut, to promote gastrointestinal motility; this activity is suggested to be responsible for the gastrointestinal prokinetic effects of certain macrolide antibiotics (often called motilides; e.g. erythromycin, azithromycin), although for many of these molecules the evidence is sparse. Relatively high doses may induce vomiting and in humans, nausea.

scholarly journals Motilin receptor (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Anthony P. Davenport ◽  
Gareth Sanger
Keyword(s):  
Amino Acid ◽  
Gastrointestinal Motility ◽  
Endocrine Cells ◽  
Phase Iii ◽  
Macrolide Antibiotics ◽  
Cholinergic Activity ◽  
Amino Acid Peptide ◽  
Motor Complex ◽  
High Doses ◽  
Motilin Receptor

Motilin receptors (provisional nomenclature) are activated by motilin, a 22 amino-acid peptide derived from a precursor (MLN, P12872), which may also generate a motilin-associated peptide. Activation of these receptors by endogenous motilin released from endocrine cells within the mucosa of the duodenum during fasting, induces propulsive phase III movements, part of the gastric migrating motor complex, and promotes the sensation of hunger. Drugs and other non-peptide compounds which activate the motilin receptor may generate a more long-lasting ability to increase cholinergic activity within the upper gut, to promote gastrointestinal motility; this activity is suggested to be responsible for the gastrointestinal prokinetic effects of certain macrolide antibiotics (often called motilides; e.g. erythromycin), although for many of these molecules the evidence is sparse. Relatively high doses of these compounds may induce vomiting and in humans, nausea.

Effect of combined citicoline and glutamate antibodies on acute, generalized convusions induced by pentylenetetrazole in mice

2018 ◽  
pp. 24-29
Author(s):  
М.Н. Карпова ◽  
Л.В. Кузнецова ◽  
Н.Ю. Клишина ◽  
Л.А. Ветрилэ
Keyword(s):  
Drug Combination ◽  
Subcutaneous Injection ◽  
Seizure Activity ◽  
Experimental Conditions ◽  
Slow Progression ◽  
Experiment Control ◽  
Effective Doses ◽  
Experimental Justification ◽  
Series Of Experiments ◽  
The Brain

Цель исследования. На 2 моделях острых генерализованных судорог (ОГС), вызванных конвульсантом пентилентетразолом (ПТЗ), изучить эффективность сочетанного применения ноотропа цитиколина - препарата с противосудорожным действием, нейрорегенеративной, нейропротекторной активностью и антител (АТ) к глутамату, обладающих противосудорожной активностью. Методика. Эксперименты выполнены на мышах-самцах линии C57Bl/6 (n = 87) массой 22-28 г. Эффективность сочетанного применения цитиколина и АТ к глутамату изучали на двух моделях ОГС. Выполнено 2 серии экспериментов. В 1-й серии ОГС вызывали внутривенным введением 1% раствора ПТЗ со скоростью 0,01 мл/с. Для изучения эффективности сочетанного применения препаратов определяли минимальное противосудорожное действие цитиколина (Цераксон, «Nicomed Ferrer Internaсional, S.A.») и АТ к глутамату при их внутрибрюшинном введении. С этой целью цитиколин вводили в дозах 500 и 300 мг/кг за 1 ч до введения ПТЗ, АТ к глутамату - в дозах 5 и 2,5 мг/кг за 1 ч 30 мин до введения ПТЗ. АТ к глутамату получали путем гипериммунизации кроликов соответствующим конъюгированным антигеном. Во 2-й серии ОГС вызывали подкожным введением ПТЗ в дозе 85 мг/кг. Для изучения эффективности сочетанного действия изучаемых препаратов последние вводили в минимально действующих дозах, установленных в 1-й серии экспериментов. Контролем во всех сериях опытов служили животные, которым вводили в аналогичных условиях и в том же объеме физиологический раствор. Результаты. Показано, что сочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах (300 и 2,5 мг/кг соответственно) при моделировании ОГС не вызывало повышения судорожной активности мозга и усиления противосудорожных свойств препаратов. Заключение. Cочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах не вызывало повышения судорожной активности мозга, что свидетельствует о безопасности совместного применения препаратов. Проведенное исследование может служить также экспериментальным обоснованием возможности использования сочетанного применения данных препаратов при судорогах с целью замедления прогрессирования нейродегенеративных процессов и благоприятного влияния на когнитивные функции. Aim. To study the effectivity of a combination of citicoline, a nootropic substance with neuroregenerative, neuroprotective, and anticonvulsant actions, and glutamate antibodies (АB) with an anticonvulsant action in two models of acute generalized convulsions (AGC) caused by the convulsant pentylenetetrazole (PTZ). Methods. Experiments were conducted on C57Bl/6 mice (n = 87) weighing 22-28 g. Effects of combined citicoline and glutamate АB were studied on two models of AGС. In the first series of experiments, AGС was induced by intravenous infusion of a 1% PTZ solution at 0.01 ml/sec. In the second series, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate efficacy of the drug combination minimum intraperitoneal anticonvulsant doses of citicoline (Tserakson, Nicomed Ferrer Internacional, S.A.) and glutamate АB were determined. To this purpose, citicoline was administered at 500 and 300 mg/kg 1 h prior to PTZ, and glutamate АB was administered at 5 and 2.5 mg/kg 90 min prior to PTZ. Glutamate АB was obtained by hyperimmunization of rabbits with a respective conjugated antigen. In the second series of experiments, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate the effect of the drug combination, the drugs were administered at the minimum effective doses determined in the first series of experiment. Control animals were injected with the same volume of saline in the same experimental conditions. Results. The combination of citicoline and glutamate AB used at minimum effective doses of 300 and 2.5 mg/kg, respectively, did not increase the seizure activity in the brain and enhanced anticonvulsant properties of the drugs in two models of AGС. Conclusion. The combination of citicoline and glutamate AT at minimum effective doses did not increase the convulsive activity in the brain, which supported safety of the drug combination. Besides, this study can serve as an experimental justification for using the drug combination in convulsions to favorably influence cognitive functions and slow progression of neurodegenerative processes.

Regional blood flow in the brain and spinal cord of hypothermic rats

1989 ◽  
Vol 257 (3) ◽  
pp. H785-H790
Author(s):  
T. Sakamoto ◽  
W. W. Monafo
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Brain Stem ◽  
Regional Blood Flow ◽  
Experimental Conditions ◽  
Pentobarbital Sodium ◽  
Arterial Blood ◽  
Group A ◽  
Group B ◽  
The Brain

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.

DeltaEF1, a zinc finger and homeodomain transcription factor, is required for skeleton patterning in multiple lineages

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 21-31 ◽  
Author(s):  
T. Takagi ◽  
H. Moribe ◽  
H. Kondoh ◽  
Y. Higashi
Keyword(s):  
Neural Crest ◽  
Zinc Finger ◽  
Intervertebral Discs ◽  
Regulatory Function ◽  
Craniofacial Abnormalities ◽  
Tarsal Bone ◽  
Skeletal Defects ◽  
Neural Crest Origin ◽  
Brain And Spinal Cord ◽  
The Brain

DeltaEF1 is a DNA binding protein containing a homeodomain and two zinc finger clusters, and is regarded as a vertebrate homologue of zfh-1 (zinc finger homeodomain-containing factor-1) in Drosophila. In the developing embryo, deltaEF1 is expressed in the notochord, somites, limb, neural crest derivatives and a few restricted sites of the brain and spinal cord. To elucidate the regulatory function of deltaEF1 in mouse embryogenesis, we generated deltaEF1 null mutant (deltaEF1null(lacZ)) mice. The deltaEF1null(lacZ) homozygotes developed to term, but never survived postnatally. In addition to severe T cell deficiency of the thymus, the deltaEF1null(lacZ) homozygotes exhibited skeletal defects of various lineages. (1) Craniofacial abnormalities of neural crest origin: cleft palate, hyperplasia of Meckel's cartilage, dysplasia of nasal septum and shortened mandible. (2) Limb defects: shortening and broadening of long bones, fusion of carpal/tarsal bone and fusion of joints. (3) Fusion of ribs. (4) Sternum defects: split and asymmetric ossification pattern of the sternebrae associated with irregular sternocostal junctions. (5) Hypoplasia of intervertebral discs. These results indicate that deltaEF1 has an essential role in regulating development of these skeletal structures. Since the skeletal defects were not observed in deltaEF1deltaC727 mice, deltaEF1 bears distinct regulatory activities which are dependent on different domains of the molecule.

Abstract 2381: Aneurysmal Subarachnoid Hemorrhage: Metabolic and Blood Flow Patterns

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
parham moftakhar ◽  
Thomas C Glenn ◽  
John Boscardin ◽  
Neil A Martin
Keyword(s):  
Blood Flow ◽  
Phase Ii ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Phase Iii ◽  
Entire Study ◽  
Cerebral Metabolic Rate ◽  
Study Population ◽  
Blood Flow Patterns ◽  
The Brain ◽  
Oxygen Difference

Objective: The purpose of this study is to classify and describe the clinically distinct metabolic and hemodynamic phases post-ASAH. Methods: 224 patients who suffered an ASAH (mean age 55±14; 74% female, 26% male) were examined. Patients underwent daily transcranial Doppler (TCD) and cerebral blood flow (CBF) studies (using 133 Xe clearance). Due to the paucity of data on post-hemorrhage day (PHD) 0, the internal carotid artery end-diastolic (ICA ED ) velocity, a surrogate for CBF, was used for the first 24 hours. The brain arteriovenous oxygen difference (AVDO 2 ) was recorded for each patient and the cerebral metabolic rate of oxygen (CMRO 2 ) was calculated. Clinical outcome was evaluated based on the Glasgow Outcome Scale (GOS) 6 months after rupture. Results: Following ASAH, 3 distinct hemodynamic phases arose for the entire study population. Phase I (hypoperfusion phase), occurs on the day of rupture (PHD 0) and is defined by a low ICA ED velocity (mean 17.8±1.1 cm/s), normal middle cerebral artery (MCA) velocity (mean V MCA 58.0±23.4 cm/s), and normal Lindegaard Ratio ([LR], mean 1.66±0.50). Phase II (relative hyperemia), (PHD 1–3), is characterized by an increasing ICA ED (mean 35.4±1.0 cm/s, p<0.0001), a relative hyperemia (mean CBF 15 40.1±1.5 ml/100g/minute, CMRO 2 1.17±0.41 ml/100g/min), a rising V MCA (mean 71.5±5.8 cm/sec, p<0.0001), and a rising but normal LR (mean 2.21±0.19, p<0.0001). During phase III (vasospasm phase, PHD 4–21), both the ICA ED and CBF decrease (mean ICA ED 19.9±0.9 cm/s, p<0.0001; mean CBF 15 36.8±0.7 ml/100g/minute, p=0.04), V MCA continues to rise (mean 107.6±2.9cm/sec, p<0.0001), and the LR is further increased (mean 3.25±0.08, p<0.0001). The CMRO 2 remains low (mean 1.17±0.40 ml/100g/min, p=1). Based on the GOS up to 90% of patients who experienced either a relative or absolute hyperemia had good outcomes. Conclusions: After an ASAH, 3 discrete metabolic and hemodynamic phases arise each with the potential for its own unique phase-specific management and therapy. Relative hyperemia, or “luxury perfusion,” during Phase II in the setting of non-elevated ICPs may provide some type of benefit for patients.

scholarly journals Role of estrogen and stress on the brain-gut axis

2019 ◽  
Vol 317 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
Yanyan Jiang ◽  
Beverley Greenwood-Van Meerveld ◽  
Anthony C. Johnson ◽  
R. Alberto Travagli
Keyword(s):  
Functional Gastrointestinal Disorders ◽  
Clinical Problem ◽  
Visceral Sensitivity ◽  
Physiological Mechanisms ◽  
Acute And Chronic Stress ◽  
Highly Correlated ◽  
The Brain ◽  
Gi Motility

Symptoms of functional gastrointestinal disorders (FGIDs), including fullness, bloating, abdominal pain, and altered gastrointestinal (GI) motility, present a significant clinical problem, with a reported prevalence of 25%–40% within the general population. More than 60% of those affected seek and require healthcare, and affected individuals report a significantly decreased quality of life. FGIDs are highly correlated with episodes of acute and chronic stress and are increased in prevalence and reported severity in women compared with men. Although there is evidence that sex and stress interact to exacerbate FGID symptoms, the physiological mechanisms that mediate these sex-dependent disparities are incompletely understood, although hormonal-related differences in GI motility and visceral sensitivity have been purported to play a significant role in the etiology. In this mini review, we will discuss brain-gut axis control of GI motility and sensitivity, the influence of estrogen on GI motility and sensitivity, and stress modulation of the brain-gut axis.

scholarly journals Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota

2020 ◽  
Vol 12 ◽  
Author(s):  
Ji Yeon Chung ◽  
Jae-Ho Jeong ◽  
Juhyun Song
Keyword(s):  
Stress Condition ◽  
Gastrointestinal Diseases ◽  
Regulatory Function ◽  
Specific Mechanism ◽  
Cns Inflammation ◽  
Natural Polyphenol ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain ◽  
Therapeutic Substance

Resveratrol is a natural polyphenol that has anti-aging and anti-inflammatory properties against stress condition. It is reported that resveratrol has beneficial functions in various metabolic and central nervous system (CNS) diseases, such as obesity, diabetes, depression, and dementia. Recently, many researchers have emphasized the connection between the brain and gut, called the gut–brain axis, for treating both CNS neuropathologies and gastrointestinal diseases. Based on previous findings, resveratrol is involved in glucagon-like peptide 1 (GLP-1) secreted by intestine L cells, the patterns of microbiome in the intestine, the 5-hydroxytryptamine (5-HT) level, and CNS inflammation. Here, we review recent evidences concerning the relevance and regulatory function of resveratrol in the gut–brain axis from various perspectives. Here, we highlight the necessity for further study on resveratrol's specific mechanism in the gut–brain axis. We present the potential of resveratrol as a natural therapeutic substance for treating both neuropathology and gastrointestinal dysfunction.

scholarly journals The Cell-Specific Pattern of Cholecystokinin Peptides in Endocrine Cells Versus Neurons Is Governed by the Expression of Prohormone Convertases 1/3, 2, and 5/6

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1600-1608 ◽  
Author(s):  
Jens F. Rehfeld ◽  
Jens R. Bundgaard ◽  
Jens Hannibal ◽  
Xiaorong Zhu ◽  
Christina Norrbom ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Peptide Hormone ◽  
Specific Pattern ◽  
Molecular Forms ◽  
Wild Type ◽  
Prohormone Convertases ◽  
Cerebral Neurons ◽  
Neuronal Processing ◽  
The Brain ◽  
Translational Product

Most peptide hormone genes are, in addition to endocrine cells, also expressed in neurons. The peptide hormone cholecystokinin (CCK) is expressed in different molecular forms in cerebral neurons and intestinal endocrine cells. To understand this difference, we examined the roles of the neuroendocrine prohormone convertases (PC) 1/3, PC2, and PC5/6 by measurement of proCCK, processing intermediates and bioactive, α-amidated, and O-sulfated CCK peptides in cerebral and jejunal extracts of null mice, controls, and in the PC5/6-expressing SK-N-MC cell-line. In PC1/3 null mice, the synthesis of bioactive CCK peptide in the gut was reduced to 3% of the translational product, all of which was in the form of α-amidated and tyrosine O-sulfated CCK-22, whereas the neuronal synthesis in the brain was largely unaffected. This is opposite to the PC2 null mice in which only the cerebral synthesis was affected. SK-N-MC cells, which express neither PC1/3 nor PC2, synthesized alone the processing intermediate, glycine-extended CCK-22. Immunocytochemistry confirmed that intestinal endocrine CCK cells in wild-type mice express PC1/3 but not PC2. In contrast, cerebral CCK neurons contain PC2 and only little, if any, PC1/3. Taken together, the data indicate that PC1/3 governs the endocrine and PC2 the neuronal processing of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22. The results suggest that the different peptide patterns in the brain and the gut are due to different expression of PCs.

scholarly journals Complex phosphorylation activity in neurosecretosomal membranes isolated from ox neurohypophyses

1980 ◽  
Vol 188 (3) ◽  
pp. 657-666 ◽  
Author(s):  
M Treiman ◽  
S Worm-Petersen ◽  
N A Thorn
Keyword(s):  
Cyclic Amp ◽  
Gel Electrophoresis ◽  
Major Part ◽  
Sodium Dodecyl ◽  
Experimental Conditions ◽  
Pituitary Glands ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain ◽  
Soluble Components

Homogenates of neural lobes of bovine pituitary glands were fractionated on Ficoll gradients to yield neurosecretosomes (nerve endings). The neurosecretosomes were lysed in a hypo-osmotic buffer and the membranes were separated from the soluble components by centrifugation. On incubation with [gamma-32P]ATP this membrane preparation showed an endogenous phosphorylation activity, which was studied by means of gel electrophoresis in the presence of sodium dodecyl sulphate, and subsequent autoradiography. The major part of the [32P]Pi detected on the gel was shown to be incorporated into three protein bands, termed A, B and C, with minimal mol.wts. of 83 000, 59 000 and 47 000 respectively. The phosphorylation of these three proteins was studied under a variety of experimental conditions. The patterns obtained were partly similar. However, important individual differences were noted, particularly with respect to the effects of cyclic AMP, Mg2+ and Ca2+. On the basis of these differences, it is suggested that in this system the phosphorylation activity is heterogenous, bands A, B and C each reflecting the presence of a different site of phosphate turnover. The relationship of bands A, B and C to several of the previously described phosphoproteins in the brain is discussed.

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