Article
Psychiatry
Angharad N. de Cates, Marieke A. G. Martens, Lucy C. Wright, Cassandra D. Gould van Praag, Liliana P. Capitao, Daisy Gibson, Philip J. Cowen, Catherine J. Harmer, Susannah E. Murphy
Summary: Depression is a prevalent illness with global impact. Current antidepressants are ineffective for a significant portion of patients, and 5-HT4 receptor agonists show potential in animal models and cognitive deficits. This study found that the 5-HT4 partial agonist prucalopride improved accuracy in identifying emotional faces in healthy participants, and inhibited activation in regions corresponding to the default mode network. However, there was no evidence of a positive bias in the neural processing of emotional faces with prucalopride treatment.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Psychiatry
Angharad N. de Cates, Lucy C. Wright, Marieke A. G. Martens, Daisy Gibson, Cagdas Turkmen, Nicola Filippini, Philip J. Cowen, Catherine J. Harmer, Susannah E. Murphy
Summary: In this study, short-term administration of the 5-HT4 partial agonist prucalopride improved memory performance and increased hippocampal and angular gyrus activity in healthy individuals, suggesting the potential of 5-HT4 receptor activation for cognitive enhancement in humans.
TRANSLATIONAL PSYCHIATRY
(2021)
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
Ulrich Gergs, Hannes Jacob, Pauline Braekow, Britt Hofmann, Steffen Pockes, Laura J. Humphrys, Uwe Kirchhefer, Charlotte Fehse, Joachim Neumann
Summary: We investigated the effects of LSD on the heart and found that it can increase the contractile force and beating rate of the atria. These effects may be mediated by the 5-HT4 receptor and H-2 histamine receptor.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Joachim Neumann, Tom Seidler, Charlotte Fehse, Margareta Marusakova, Britt Hofmann, Ulrich Gergs
Summary: The study revealed that metoclopramide had a partial agonist effect on human cardiac 5-HT4 receptors, while domperidone had no effect at all.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Gastroenterology & Hepatology
Fabio Grizzi, Marco Spadaccini, Maurizio Chiriva-Internati, Mohamed A. A. A. Hegazi, Robert S. Bresalier, Cesare Hassan, Alessandro Repici, Silvia Carrara
Summary: The morphological complexity of cells and tissues, whether normal or pathological, is characterized by irregularity and self-similarity across different scales. Fractal geometry holds promise in providing a quantitative measure of the irregularly shaped morphologies and their underlying self-similar temporal behaviors. This article explores the fractal nature of the gastrointestinal system and the potential applications of fractal geometry in clinical gastroenterology and hepatology practice.
WORLD JOURNAL OF GASTROENTEROLOGY
(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
Neurosciences
Angharad N. de Cates, Marieke A. G. Martens, Lucy C. Wright, Daisy Gibson, Gershon Spitz, Cassandra D. Gould van Praag, Sana Suri, Philip J. Cowen, Susannah E. Murphy, Catherine J. Harmer
Summary: This study found that the 5-HT4 receptor agonist prucalopride enhanced functional connectivity between regions involved in cognitive networks and reduced connectivity within the default mode network in healthy volunteers. This may explain the previously observed cognitive enhancement effects of 5-HT4 receptor agonists in humans and supports their potential use in clinical psychiatric populations.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2023)
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.
Review
Biochemistry & Molecular Biology
Natalia Roa-Vidal, Adriana Rodriguez-Aponte, Jose Lasalde-Dominicci, Coral Capo-Velez, Manuel Delgado-Velez
Summary: Macrophages play a vital role in defending the body and exhibit remarkable adaptability in response to invading pathogens and stimuli. The activation of the cholinergic anti-inflammatory pathway, especially mediated by the alpha 7-nAChR, is crucial in suppressing proinflammatory cytokines and maintaining homeostasis. This review focuses on macrophage polarization, the influence of viral infections on macrophage inflammatory phenotypes, and the emerging significance of dup alpha 7 in macrophage polarization and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Dairy & Animal Science
Antonio Palladino, Elena De Felice, Chiara Attanasio, Carmela M. A. Barone, Antonio Crasto, Livia D'Angelo, Daniela Giaquinto, Claudia Lambiase, Paola Scocco, Francesco Serrapica, Lucianna Maruccio
Summary: This study provides an integrated description of the morphology of the esophagus and stomach in Nile tilapia. The stomach is divided into five distinct zones and histological analysis revealed the presence of mucins in the esophagus and stomach. These findings contribute to a better understanding of the growth, health status, and comparison of different conditions in Nile tilapia.
Article
Pharmacology & Pharmacy
Joachim Neumann, Nils Schulz, Charlotte Fehse, Karyna Azatsian, Aneta Cinakova, Margareta Marusakova, Britt Hofmann, Ulrich Gergs
Summary: The study aimed to examine the effects of bufotenin, a hallucinogenic drug, on human cardiac serotonin 5-HT4 receptors. It was found that bufotenin can enhance the force of contraction and beating rate by stimulating the 5-HT4 receptors in both transgenic mouse cardiac preparations and human atrial preparations. This study is significant for understanding the effects of bufotenin on the heart.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(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
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)
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.