Article
Veterinary Sciences
Stephanie Rutherford, Frederic Gaschen, Roman Husnik, Jon Fletcher, Lorrie Gaschen
Summary: This study evaluated the effects of azithromycin on gastric emptying (GE) and gastric motility in healthy cats. It found that azithromycin and erythromycin both shortened GE time in a comparable manner. Further evaluation of their efficacy in cats with gastric dysmotility is warranted.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2022)
Review
Gastroenterology & Hepatology
James J. Galligan
Summary: 5-HT4 receptors are G protein-coupled receptors that activate adenylate cyclase to increase intracellular cyclic AMP levels, leading to the activation of protein kinase A. These receptors are expressed in the central and peripheral nervous systems, particularly in the enteric nervous system, where they enhance neurotransmitter release and propulsive motility. Novel 5-HT4 receptor agonists, 5-HT4-LA1 and 5-HT4-LA-2, stimulate colonic motility locally without being absorbed systemically, demonstrating prokinetic actions in the GI tract.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Gastroenterology & Hepatology
John R. Konen, Melody M. Haag, Daria Guseva, Molly Hurd, Alisha A. Linton, Brigitte Lavoie, Colleen B. Kerrigan, Emily Joyce, Stephan C. Bischoff, Steve Swann, Luana Griffin, Jun Matsukawa, Matthew D. Falk, Tony S. Gibson, Grant W. Hennig, Jill Wykosky, Gary M. Mawe
Summary: Stimulation of epithelial 5-HT(4)Rs can enhance propulsive motility, indicating mucosal 5-HT(4)Rs may represent a safe and effective therapeutic target for constipation treatment.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Review
Pharmacology & Pharmacy
Michael Camilleri, Jessica Atieh
Summary: Prokinetic agents enhance gastrointestinal muscular contractions to improve transit of intra-luminal content. Metoclopramide is the only FDA-approved medication for gastroparesis in the United States, while domperidone can be prescribed through a special program. Newer agents are being developed targeting different gastric motor functions.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ulrich Gergs, Tobias Brueckner, Britt Hofmann, Joachim Neumann
Summary: The study revealed that lowering temperature can increase arrhythmias in mice overexpressing the human 5-HT4 receptor in their cardiac myocytes, suggesting a potential link between 5-HT4 receptors and hypothermia-induced arrhythmias in human patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Kazumi Inokuchi, Tatsuhiro Masaoka, Takanori Kanai
Summary: Prokinetics is a limited therapeutic option for functional and motility disorders of the stomach, while Kampo medicine, especially herbs like rikkunshito, offers alternative treatment with diverse therapeutic mechanisms. The increasing evidence for the efficacy of herbal medicine in treating stomach disorders highlights the potential of herbal medicine as a valuable therapeutic option.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sunho Choi, Min Jung Lee, Kwang-Hyun Ahn
Summary: Novel 4-methylpiperidinyl benzamide derivatives were synthesized and evaluated for their prokinetic activities. Compound 28b showed potent receptor-binding affinity, improved safety profiles, and enhanced gastric emptying rate in in vivo rat models, making it a promising candidate for treating gastrointestinal disorders.
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
J. Daniel Bailey, Edward Helbling, Amey Mankar, Matthew Stirling, Fred Hicks, David K. Leahy
Summary: Reducing or eliminating organic solvent use in pharmaceutical manufacturing is a highly effective way to reduce environmental, health, and safety impacts. The process described utilizing primarily water-based methods significantly reduces material inputs and organic solvent use, while surprisingly using less water and improving overall yield compared to traditional methods.
Article
Pharmacology & Pharmacy
Dae Young Lee, Hee Eun Kang
Summary: This study validated a quantitative assay for DA-6886 in rat plasma and evaluated its pharmacokinetics and tissue distribution in rats. The results showed that DA-6886 distributed extensively in the liver, kidney, lung, and digestive tract, and exhibited nonlinear pharmacokinetics after oral administration.
Article
Gastroenterology & Hepatology
Nick Goelen, Mike Jones, I-Hsuan Huang, Florenca Carbone, Pieter Janssen, Jan Tack
Summary: Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. The association between symptom improvement and acceleration of gastric emptying (GE) by prokinetic agents is not clear. This meta-analysis aimed to provide a transparent update on the association between symptom improvement and GE acceleration in patients with gastroparesis.
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Alejandro Castro-Alvarez, Emigdio Chavez-Angel, Ronald Nelson
Summary: This study analyzed a series of active compounds in the 5-HT4 receptor using quantitative structure-activity relationship, leading to the design of novel 5-HT4 partial agonists with potential biological activity. The research provided new insights for the design and development of new therapeutic options for neurodegenerative disorders like Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Pierre Lecouflet, Candice M. Roux, Brigitte Potier, Marianne Leger, Elie Brunet, Jean-Marie Billard, Pascale Schumann-Bard, Thomas Freret
Summary: Activation of the 5-HT4R has been shown to impact LTP within the hippocampal CA1 area through modulation of GABAergic neurotransmission. The study also revealed the involvement of GABA(B) receptor in this regulatory process.
Article
Biochemistry & Molecular Biology
Ulrich Gergs, Timo Gerigk, Jonas Wittschier, Constanze T. Schmidbaur, Clara Rottger, Mareen Mahnkopf, Hanna Edler, Hartmut Wache, Joachim Neumann
Summary: The study found that cardiac function is affected by 5-HT4 receptor overexpression under pathophysiological conditions, with potential benefits or drawbacks depending on the type of stress. 5-HT4 receptor overexpression influenced the response of the heart to hypoxia and ischemia, as well as cardiac hypertrophy.
Article
Biochemistry & Molecular Biology
Hannes Jacob, Pauline Braekow, Rebecca Schwarz, Christian Hoehm, Uwe Kirchhefer, Britt Hofmann, Joachim Neumann, Ulrich Gergs
Summary: Ergotamine is a tryptamine-related alkaloid used to treat migraines. It has positive inotropic effects on both 5-HT4-serotonin receptors and H-2-histamine receptors in the human heart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eri Kitayama, Maki Kimura, Takehito Ouchi, Masahiro Furusawa, Yoshiyuki Shibukawa
Summary: This study investigated the dynamics of intracellular cAMP in cultured human odontoblasts to understand the detailed expression patterns and role of the intracellular cAMP signaling pathway. The results showed the presence of G(alpha)s protein and various receptors (IP, 5-HT4, D-1, A(2A), and VIP) in odontoblasts. Activation of these receptors increased intracellular cAMP levels by activating AC, and this increase was inhibited by an AC inhibitor and receptor antagonists.
Article
Pharmacology & Pharmacy
Weigang Cai, Raj Makwana, Marilisa Straface, Armen Gharibans, Paul L. R. Andrews, Gareth J. Sanger
Summary: The mouse isolated stomach exhibited myogenic contractions that were resistant to neural activity blockade by TTX. Compounds blocking interstitial cells of Cajal activity or atropine could prevent or reduce these contractions in the presence of TTX, while neostigmine enhanced the contractions (which were antagonized by atropine), suggesting the involvement of non-neuronal acetylcholine in their regulation.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Gareth J. Sanger
Summary: The gastrointestinal hormone motilin helps control stomach movements during hunger and promotes hunger in humans. While motilin and its receptor genes have undergone pseudonymization in rodents, some studies suggest low concentrations of motilin can still function in the gastrointestinal tract and central nervous system of these animals.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Pharmacology & Pharmacy
Marilisa Straface, Marie -Ange Koussai, Raj Makwana, Ellie Crawley, Alexandra Palmer, Weigang Cai, Armen Gharibans, Miriam Adebibe, John Loy, Greg O'Grady, Paul L. R. Andrews, Gareth J. Sanger
Summary: Software was developed to measure muscle tone and parameters defining contractions in human stomach. The study found that only E-4031 and CaCC blockers influenced myogenic contractions, not muscle tone.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Cristina Perez-Ternero, Aisah A. Aubdool, Raj Makwana, Gareth J. Sanger, Roland H. Stimson, Li F. Chan, Amie J. Moyes, Adrian J. Hobbs
Summary: C-type natriuretic peptide (CNP) plays a crucial role in lipid homeostasis and energy balance by regulating the expression of uncoupling protein-1 and lipid utilization. CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming and reducing peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression, while driving adipogenesis via NPR-B/protein kinase-G.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Nicholas Baidoo, Ellie Crawley, Charles H. Knowles, Gareth J. Sanger, Abi Belai
Summary: Ageing alters the total collagen content and distribution in the human colon, with a significant increase in total collagen content in the submucosa and muscularis externa of the elderly. These changes may lead to a loss of function.
Letter
Pharmacology & Pharmacy
Gareth J. Sanger, Paul L. R. Andrews
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Raj Makwana, Ellie Crawley, Marilisa Straface, Alexandra Palmer, Armen Gharibans, Kalpana Devalia, John Loy, Greg O'Grady, Paul L. R. Andrews, Gareth J. Sanger
Summary: This study investigated the effects of vasopressin and adrenaline on human gastric muscle and found that they increase gastric muscle tone and spontaneous muscle contractions, potentially leading to nausea.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Nicholas Baidoo, Gareth J. Sanger, Abi Belai
Summary: Old age is associated with a higher incidence of lower bowel conditions such as constipation. This study assessed and compared the pattern of distribution of enteric glial cells (EGCs) in adult and elderly human colon. The results showed that aging does not result in a loss of Sox-10-IR EGCs in the myenteric plexus (MP) and submucosal plexus (SMP), but reduces S100-IR EGCs density within the musculature, which may contribute to colonic dysfunction.
Article
Cell Biology
Nicholas Baidoo, Gareth J. Sanger, Abi Belai
Summary: This study found that the total collagen content in the colonic wall, particularly in the taenia coli, increases with age. This increase may affect the tensile strength of the colon.
Review
Gastroenterology & Hepatology
Gareth J. Sanger, Paul L. R. Andrews
Summary: This study summarizes the drugs used to treat gastroparesis and explores the rationale behind blocking different pathways causing vomiting and increasing gastric emptying via different mechanisms. The results suggest that some drug classes lack scientific rationale for inhibiting vomiting. NK1 antagonism shows some rationale but limited efficacy against nausea. The efficacy of selective 5-HT4 agonists varies. Further research is needed to develop novel approaches targeting nausea and objective assessments of nausea.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Letter
Gastroenterology & Hepatology
Gareth J. Sanger, Paul L. R. Andrews
Article
Pharmacology & Pharmacy
Raj Makwana, Gareth J. Sanger
Summary: Interstitial cells of Cajal generate slow wave gastric electrical activity, initiating spontaneous muscle contractions. This becomes dysrhythmic during nausea when [Arg8]-vasopressin (AVP) is also released. In human stomach AVP increased spontaneous contraction activity and muscle tone, not neuronally-mediated contractions. Rodents cannot vomit, releasing the related hormone, oxytocin (OT) instead. We hypothesised that rat stomach would behave differently.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Medicine, Research & Experimental
Cristina Perez-Ternero, Aisah Aubdool, Raj Makwana, Gareth Sanger, Roland Stimson, Li Chan, Amie Moyes, Adrian Hobbs
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Raj Makwana, Ellie Crawley, Marilisa Straface, Armen Gharibans, Kalpana Devalia, John Loy, Greg O'Grady, Paul L. R. Andrews, Gareth Sanger
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Nicholas Baidoo, Gareth J. Sanger, Abi Belai
Summary: This article introduces a laboratory protocol using image analysis to quantify the collagen content in the colon. It provides a systematic and reproducible method for accurately assessing the spatial distribution and localization of collagen fibers in formalin-fixed, paraffin-embedded samples. The protocol is also useful for retrospective studies.