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.

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 (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Anthony P. Davenport
Keyword(s):  
Amino Acid ◽  
Gastrointestinal Motility ◽  
Macrolide Antibiotics ◽  
Amino Acid Peptide ◽  
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. These receptors promote gastrointestinal motility and are 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.

Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

2019 ◽  
Vol 16 ◽  
Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mrna Expression ◽  
Surface Expression ◽  
Phase Iii ◽  
Cell Surface Expression ◽  
Optimum Dose ◽  
High Dose ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
High Doses

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

scholarly journals Neuromedin U receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Khaled Al-hosaini ◽  
Stephen R. Bloom ◽  
Joseph Hedrick ◽  
Andrew Howard ◽  
Preeti Jethwa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Amino Acid ◽  
Species Differences ◽  
Fetal Liver ◽  
Single Gene ◽  
Acid Product ◽  
Amino Acid Peptide ◽  
Upper Gastrointestinal ◽  
Sole Product

Neuromedin U receptors (provisional nomenclature as recommended by NC-IUPHAR [29]) are activated by the endogenous 25 amino acid peptide neuromedin U (neuromedin U-25, NmU-25), a peptide originally isolated from pig spinal cord [90]. In humans, NmU-25 appears to be the sole product of a precursor gene (NMU, P48645) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (neuromedin S-33) has also been identified as an endogenous agonist [95]. NmS-33 is, as its name suggests, a 33 amino-acid product of a precursor protein derived from a single gene and contains an amidated C-terminal heptapeptide identical to NmU. NmS-33 appears to activate NMU receptors with equivalent potency to NmU-25.

Randomized Comparison of Standard Induction with Daunorubicin (DNR) for 3 Days vs Idarubicin (IDA) for 3 or 4 Days in AML pts Aged 50 to 70 and of Maintenance with Interleukin 2. Final Analysis of the ALFA 9801 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 162-162 ◽  
Author(s):  
Cecile Pautas ◽  
Xavier Thomas ◽  
Fatiha Merabet ◽  
Emmanuel Raffoux ◽  
Jean Henri Bourhis ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Final Analysis ◽  
Risk Groups ◽  
Salvage Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Duration Of Hospitalization ◽  
High Doses ◽  
Grade 3 ◽  
To Receive

Abstract Background: For many years the ALFA Group has used high dose DNR, i.e 80 mg/m2/day for 3d as part of the induction regimen for untreated adult AML pts. As the equivalence of DNR and Ida is not known we conducted a phase III study to compare high dose DNR to Ida. We also tested the effect of IL2 for maintenance. Methods: Newly diagnosed AML, aged 50 to 70 years, were randomized to receive AraC 200 mg/m2/day IV x 7 d with either DNR: 80 mg/m2/d x 3 d (arm 1) or Ida: 12 mg/m2/d x 3 d (arm 2) or x 4 d (arm 3). Pts who failed could receive a salvage course with Mitoxantrone x 2 d and AraC1g/m2 12 hrs x 4d. Response was assessed after induction+/− salvage chemotherapy. CR pts received 2 consolidation courses according to the induction arm with DNR: 80 mg/m2 or Ida:12 mg/m2 for 1 day (first course) or 2 days (2nd course) and AraC:1g/m2/12 hrs x 4 days. Pts in CCR after the two consolidation courses were randomized to receive or not a maintenance immunotherapy with IL2: 5.106/m2 for 5 days monthly for12 months. Results: From 2001 to 2006, 468 pts were included (median age: 60 years). The 3 treatment arms were well matched for pretreatment characteristics. CR was achieved in 360/468 pts (77%): 109 (70%) pts arm 1, 129 (83%) arm 2, 122 (78%) arm 3 (p=0.02).70 pts, (45%) pts in the DNR arm reached CR after 1 course vs 97 (62%) and 90 (57%) in Ida arms (p= 0.006). Pts in Ida arms experienced more grade 3 or 4 mucositis (p=0.004) but no differences were observed between the 3 arms for duration of hospitalization, time to PMN or plts recovery, incidence of grade 3 or 4 infectious episodes and treatment related mortality. 3 year cumulative incidence of relapse was 69%, 63%, 62% resp in arms 1,2,3 (p=NS). 3 year EFS was 19%, 30%, 26% resp (p=0.06 for arm 1 vs arms 2 and 3). 3 year OS was 31%, 40% 41% resp in arms 1,2,3 (p=NS). Age (< or >60 years), sex, initial WBC counts, initial LDH (nl or >nl), DNR or Ida arms, need for a salvage course were not predictive for relapse, while 2yCIR was 43%, 64%, 77% among respectively fav, intermediate and unfav cytogenetic risk groups resp (p=0.0046). Of the 219 pts alive in CR after consolidations, 161 (73%) were randomized for maintenance. Only 22 of the 77 pts randomized for IL2 completed the 1 year treatment. 32 and 23 pts stopped IL2 resp because of relapse or intolerance. There were no differences in relapse or OS in both maintenance arms. Conclusion: Ida treatment even when compared to high doses of DNR yields higher CR rate and more CR after one course. This effect translated in slightly better EFS but not better CIR or OS. IL2 maintenance treatment at least as scheduled in this trial was difficult to apply and showed no impact on disease course.

scholarly journals The Role of Ghrelin in Anorexia Nervosa

2018 ◽  
Vol 19 (7) ◽  
pp. 2117 ◽  
Author(s):  
Martha Schalla ◽  
Andreas Stengel
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Endocrine Cells ◽  
Body Weight Gain ◽  
Treatment Strategies ◽  
Peptide Hormone ◽  
Future Research ◽  
Amino Acid Peptide ◽  
Pronounced Reduction

Ghrelin, a 28-amino acid peptide hormone expressed in X/A-like endocrine cells of the stomach, is the only known peripherally produced and centrally acting peptide that stimulates food intake and therefore attracted a lot of attention with one major focus on the treatment of conditions where an increased energy intake or body weight gain is desired. Anorexia nervosa is an eating disorder characterized by a pronounced reduction of body weight, a disturbed body image and hormonal alterations. Ghrelin signaling has been thoroughly investigated under conditions of anorexia nervosa. The present review will highlight these alterations of ghrelin in anorexia and discuss possible treatment strategies targeting ghrelin signaling. Lastly, gaps in knowledge will be mentioned to foster future research.

Motilin and the postprandial motility of the antrum

1992 ◽  
Vol 70 (11) ◽  
pp. 1491-1495 ◽  
Author(s):  
M. Boivin ◽  
M. Riberdy ◽  
M. -C. Raymond ◽  
L. Trudel ◽  
P. Poitras
Keyword(s):  
Contractile Response ◽  
Plasma Concentrations ◽  
Phase Iii ◽  
Gastrointestinal Hormone ◽  
Postprandial Period ◽  
Postprandial Motility ◽  
Smooth Muscle Function ◽  
Plasma Motilin ◽  
Erythromycin Lactobionate ◽  
Motilin Receptor

This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 μg∙kg−1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin.Key words: antral motility, gastrointestinal hormone, gastrointestinal motility, motilin, regulatory peptide, smooth muscle function.

Effect of atropine on pancreatic response to HCl and secretin

1981 ◽  
Vol 240 (5) ◽  
pp. G376-G380 ◽  
Author(s):  
M. V. Singer ◽  
T. E. Solomon ◽  
H. Rammert ◽  
F. Caspary ◽  
W. Niebel ◽  
...  
Keyword(s):  
Atropine Sulfate ◽  
Secretory Response ◽  
Low Doses ◽  
Cholinergic Activity ◽  
Pancreatic Fistulas ◽  
High Doses ◽  
Protein Response ◽  
Dose Dependent Increase ◽  
Protein Output ◽  
Dose Dependent

In dogs with gastric and pancreatic fistulas, we studied the effect of atropine on the pancreatic secretory response to secretin and intestinal HCl. Atropine sulfate (20 micrograms.kg-1.h-1 iv) significantly depressed basal bicarbonate and protein output. Atropine depressed bicarbonate responses to low doses (62.5, 125, 250, and 500 ng.kg-1.h-1) of secretin but had no significant effect on responses to high doses (1,000 and 2,000 ng.kg-1.h-1). Secretin, with or without atropine, did not stimulate pancreatic protein output above basal. Atropine depressed bicarbonate responses to low loads (3, 6, and 12 mmol.h-1) of HCl but had no significant effect on responses to high loads (12, 24, and 48 mmol.h-1). Intraduodenal HCl produced a dose-dependent increase in protein output. Atropine abolished protein responses to low loads (3 and 6 mmol.h-1) but did not affect responses to high loads (24 and 48 mmol.h-1) of HCl. These findings are compatible with the hypotheses that a) endogenous cholinergic activity augments the pancreatic bicarbonate response to secretin, and b) the pancreatic protein response to intraduodenal HCl is, at least in part, mediated cholinergically.

Limb regeneration blastema cells in the adult newt, Notophthalmus viridescens, give aberrant response to colchicine

1983 ◽  
Vol 61 (3) ◽  
pp. 553-559 ◽  
Author(s):  
Brenda L. Coomber ◽  
Karin J. Davidson ◽  
Steven R. Scadding
Keyword(s):  
Body Weight ◽  
Mitotic Index ◽  
Treatment Time ◽  
Limb Regeneration ◽  
Duodenal Mucosa ◽  
Index Number ◽  
High Doses ◽  
Mitotic Figures ◽  
Regeneration Blastema ◽  
Newt Limb

This study was designed to investigate the effect of colchicine on the mitotic index (number of mitotic figures per 1000 cells) in the newt limb regeneration blastema. Colchicine doses from 0.1 to 1000 μg per gram body weight and treatment durations from 2 to 72 h were used to determine the dose of colchicine and treatment period resulting in optimum metaphase arrest. A preliminary experiment demonstrated that there was no circadian rhythm of mitosis in the newt limb regeneration blastema. A dose of 5 μg colchicine per gram body weight was found to give the maximum mitotic index; both higher and lower doses had less effect. Very high doses of colchicine resulted in a mitotic index the same as that of the controls. The mitotic index increased with increasing treatment time up to 36 h, after which there was no further increase. In other newt tissues such as duodenal mucosa and liver, a more typical dose–response relationship was observed in that increased colchicine dose led to increased mitotic indices up to the level of lethal doses of colchicine.

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