Article
Chemistry, Multidisciplinary
Prashant Donthamsetti, David B. Konrad, Belinda Hetzler, Zhu Fu, Dirk Trauner, Ehud Y. Isacoff
Summary: G protein-coupled receptors (GPCRs) are common drug discovery targets, but the complexity of in vivo receptor activation has hindered drug development. Photopharmacology offers the potential to control drug action using light. Recent advances include a photoswitchable allosteric agonist that selectively activates receptors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Pharmacology & Pharmacy
Sam Groom, Nina K. Blum, Alexandra E. Conibear, Alexander Disney, Rob Hill, Stephen M. Husbands, Yangmei Li, Lawrence Toll, Andrea Kliewer, Stefan Schulz, Graeme Henderson, Eamonn Kelly, Chris P. Bailey
Summary: This study confirmed that Compound 1 is a G protein-biased mu agonist that can induce substantial rapid receptor desensitisation in mammalian neurons. However, contrary to previous assumptions, the desensitisation effect of Compound 1 is dependent on G protein-coupled receptor kinase (GRK).
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Wei Xu, Frank Bearoff, Sandhya Kortagere
Summary: This study demonstrates that biased signaling agonists of D3R have differential effects on ERK1/2, which may be advantageous for the development of better drugs.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Parthasaradhireddy Tanguturi, Vibha Pathak, Sixue Zhang, Omar Moukha-Chafiq, Corinne E. Augelli-Szafran, John M. Streicher
Summary: The study successfully developed novel inverse agonists and irreversible antagonists for the delta opioid receptor, providing new tools to investigate its biology or potential therapeutics.
Article
Pharmacology & Pharmacy
Nokomis Ramos-Gonzalez, Sam Groom, Katy J. Sutcliffe, Sukhvinder Bancroft, Chris P. Bailey, Richard B. Sessions, Graeme Henderson, Eamonn Kelly
Summary: The illicit use of fentanyl-like drugs and the resulting overdose deaths is a major problem. This study compared the efficacy and signaling bias of different fentanyls, and found that carfentanil is biased towards beta-arrestin.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Claire Normand, Billy Breton, Marine Salze, Eric Barbeau, Arturo Mancini, Martin Audet
Summary: Prostaglandins are bioactive lipids involved in various physiological and pathophysiological processes. This study investigated the signaling profiles of different isoforms of the human EP3 receptor, which is activated by the bioactive lipid PGE2. The research revealed potential differences in signaling mechanisms between isoforms and identified a specific antagonist with biased agonist effects on the Gαz pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Jeffrey F. Diberto, Katie Smart, Reid H. J. Olsen, Bryan L. Roth
Summary: TRUPATH is a platform based on bioluminescence resonance energy transfer for quantifying G protein-coupled receptor activity via dissociation of heterotrimeric G protein biosensors. Protocols for agonist and antagonist TRUPATH assays in the 384-well plate format are provided, offering higher throughput capabilities.
Article
Engineering, Biomedical
Mouna Ghedira, Inke Marie Albertsen, Valentina Mardale, Catherine-Marie Loche, Maria Vinti, Jean-Michel Gracies, Nicolas Bayle, Emilie Hutin
Summary: In hemiparesis during the swing phase, there is higher activation of agonists and antagonists on the paretic side compared to the non-paretic side, leading to altered muscle activation patterns and reduced ankle dorsiflexion and knee flexion.
CLINICAL BIOMECHANICS
(2021)
Article
Pharmacology & Pharmacy
Cai Read, Duuamene Nyimanu, Peiran Yang, Rhoda E. Kuc, Thomas L. Williams, Christopher M. Fitzpatrick, Richard Foster, Robert C. Glen, Janet J. Maguire, Anthony P. Davenport
Summary: CMF-019, a small molecule apelin agonist, demonstrates strong vasodilatory effects in vivo and protects human pulmonary artery endothelial cells from apoptosis. It exhibits remarkable bias at the apelin receptor and could serve as the basis for designing novel therapeutic agents for chronic diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Jia Duan, Heng Liu, Fenghui Zhao, Qingning Yuan, Yujie Ji, Xiaoqing Cai, Xinheng He, Xinzhu Li, Junrui Li, Kai Wu, Tianyu Gao, Shengnan Zhu, Shi Lin, Ming-Wei Wang, Xi Cheng, Wanchao Yin, Yi Jiang, Dehua Yang, H. Eric Xu
Summary: Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) regulates G-protein and arrestin signalling, which can be modulated by biased ligands. However, the molecular assembly of GRKs on GPCRs and the mechanisms of GRK-mediated biased signalling are not well understood. This study presents the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Ga-q, and the arrestin-biased ligand SBI-553. The structure provides insights into the details of GPCR-GRK interactions and the mechanisms underlying GRK2-mediated biased signalling.
Article
Chemistry, Medicinal
Sharon Cabanu, Fuencisla Pilar-Cuellar, Paula Zubakina, Eva Florensa-Zanuy, Julia Senserrich, Adrian Newman-Tancredi, Albert Adell
Summary: Depression, the most prevalent mental illness, is believed to be associated with serotonin (5-HT) neurotransmitter. In this study, NLX-101 showed antidepressant-like effects by increasing extracellular concentrations of glutamate and dopamine, and regulating the activation of several signaling pathways and gene expression.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wang, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: This study reports a new binding mode between a G protein and its receptor, involving a specific small-molecule agonist. The high-resolution structure of the complex is determined, providing insights for designing small-molecule agonists for class B G-protein-coupled receptors.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wu, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.
Article
Pharmacology & Pharmacy
Jose A. Pino, Gabriel Nunez-Vivanco, Gabriela Hidalgo, Miguel Reyes Parada, Habibeh Khoshbouei, Gonzalo E. Torres
Summary: This study reveals that G protein beta gamma subunits can bind to the dopamine transporter (DAT) and activate DAT-mediated dopamine efflux, similar to the mechanism of action of psychostimulants like amphetamine (AMPH). Through a combination of computational biology, mutagenesis, biochemical, and functional assays, the amino acid residues within the 582-596 sequence of the DAT carboxy terminus involved in the DAT-G beta gamma interaction and G beta gamma-induced dopamine efflux were identified. Residues like R588 and F587 within the carboxy terminus of DAT play critical roles in the physical interaction between DAT and G beta gamma, influencing dopamine efflux.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Andreas Bock, Marcel Bermudez
Summary: Bias agonism in GPCRs is likely a result of preferential allosteric coupling from the ligand binding pocket to a specific transducer, leading to selective activation of desired signaling pathways and potentially reducing side effects.
Article
Neurosciences
Massimo Pierucci, Francis Delicata, Roberto Colangeli, Antonella Marino Gammazza, Alessandro Pitruzzella, Maurizio Casarrubea, Philippe De Deurwaerdere, Giuseppe Di Giovanni
Summary: This study found that nicotine-induced neuronal activity in the VTA is regulated by the LHb region, with acute and chronic nicotine having different effects on VTA DA neurons.
Review
Biochemistry & Molecular Biology
Abdeslam Chagraoui, Giuseppe Di Giovanni, Philippe De Deurwaerdere
Summary: The discovery of the D3 receptor has sparked interest in the field of neurological diseases, particularly Parkinson's disease. This article discusses the role of D3 receptors in Parkinson's disease and their relationship with current treatments, highlighting the potential interactions between D1 and D3 receptors that may contribute to motor side effects.
Letter
Neurosciences
Daniel Cassar, Manuela Radic, Maurizio Casarrubea, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: In this study, GAERS and NEC rats were treated with the CB1/2 receptor agonist WIN 55,212-2 (2 mg/kg) and tested on the Elevated Plus-Maze.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Philippe De Deurwaerdere, Giuseppe Di Giovanni
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Philippe De Deurwaerdere, Maurizio Casarrubea, Daniel Cassar, Manuela Radic, Emilie Puginier, Abdeslam Chagraoui, Giuseppe Crescimanno, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: Childhood absence epilepsy is often accompanied by neuropsychological comorbidities such as anxiety. This study found that the synthetic cannabinoid receptor agonist WIN 55,212-2 had strain-dependent effects on anxiety-like and motor behavior in rats with absence epilepsy. The study also revealed alterations in cerebral monoaminergic levels in these rats, suggesting a role of endocannabinoids and monoamines in the comorbidities.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Virginie Marty, Jasmine J. Butler, Coutens Basile, Oumaima Chargui, Abdeslam Chagraoui, Bruno P. Guiard, Philippe De Deurwaerdere, Jerome Cavaille
Summary: The absence of Snord115 affects central monoaminergic circuits, but does not elicit gross behavioral abnormalities.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Franck Aby, Louis-Etienne Lorenzo, Zoe Grivet, Rabia Bouali-Benazzouz, Hugo Martin, Stephane Valerio, Sara Whitestone, Dominique Isabel, Walid Idi, Otmane Bouchatta, Philippe De Deurwaerdere, Antoine G. Godin, Cyril Herry, Xavier Fioramonti, Marc Landry, Yves De Koninck, Pascal Fossat
Summary: Research has shown that serotonin (5-HT) neurons have a pain-relieving effect in mice who have not experienced pain before, but become pain-promoting in neuropathic pain models. An imbalance in spinal KCC2 function turns this pain relief into pain promotion, but KCC2 enhancers can restore the pain-relieving effect. Additionally, combining selective serotonin reuptake inhibitors (SSRIs) with KCC2 enhancers can effectively relieve pain hypersensitivity caused by nerve injury.
Article
Biochemistry & Molecular Biology
Hugo Martin, Sebastien Bullich, Maud Martinat, Mathilde Chataigner, Mathieu Di Miceli, Vincent Simon, Samantha Clark, Jasmine Butler, Mareike Schell, Simran Chopra, Francis Chaouloff, Andre Kleinridders, Daniela Cota, Philippe De Deurwaerdere, Luc Penicaud, Sophie Laye, Bruno P. Guiard, Xavier Fioramonti
Summary: Insulin directly modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and control emotional behaviors. However, in T2D animal models, the anxiolytic effect of intranasal insulin and the response of 5-HT neurons to insulin are both blunted.
MOLECULAR PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Hugo R. Arias, Philippe De Deurwaerdere, Ali El-Kasaby, Giuseppe Di Giovanni, Sanung Eom, Junho H. Lee, Michael Freissmuth, Abdeslam Chagraoui
Summary: The antidepressant-like activity of (+)-catharanthine and (-)-18-methoxycoronaridine was studied in male and female mice using forced swim and tail suspension tests. The results showed that both compounds induced similar antidepressant-like activity, with (+)-catharanthine also increasing climbing behavior and mobilizing norepinephrinergic neurotransmission. In vitro studies demonstrated that both compounds inhibit serotonin transporter, while (+)-catharanthine also inhibits norepinephrine transporter with higher potency.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Maurizio Casarrubea, Manuela Radic, Tatiana Pinto Morais, Erika Mifsud, Eleonora Cuboni, Stefania Aiello, Giuseppe Crescimanno, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: The study compared Genetic Absence Epilepsy Rats from Strasbourg (GAERS), non-epileptic control (NEC), and Wistar rats bred under the same conditions, along with commercially available Wistar rats (Cm Wistar) as a control. The results showed that male GAERS rats lacked comorbid anxiety, and the study emphasized the importance of using Wistar rats from the same breeding conditions.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Hugo R. Arias, Philippe De Deurwaerd, Petra Scholze, Seiji Sakamoto, Itaru Hamachi, Giuseppe Di Giovanni, Abdeslam Chagraoui
Summary: The sedative and anxiolytic-like activity of two coronaridine congeners was studied in mice. The results showed that these compounds induce sedative and anxiolytic effects by increasing GABAA receptor affinity for GABA through a benzodiazepine-independent mechanism.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.
