Review
Medicine, Research & Experimental
Miroslav Adzic, Iva Lukic, Milos Mitic, Emilija Glavonic, Nina Dragicevic, Sanja Ivkovic
Summary: Major depressive disorder (MDD) affects approximately 5% of the world population, and a significant percentage of patients do not achieve complete remission with classical antidepressant medications. Recent evidence suggests that targeting opioid receptors may offer effective therapeutics for stress-related psychiatric disorders. The dysregulation of opioid signaling in depression and the success of opioid modulation in preclinical studies and clinical trials highlight the potential of opioids as adjuvant or alternative treatments for depression. However, further research is needed to fully understand the benefits and weaknesses of opioid system modulation in depression.
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
Neurosciences
Katherine E. Barker, Alynn J. Lecznar, Jill M. Schumacher, Jeffrey S. Morris, Howard B. Gutstein
Summary: Research has shown that subanalgesic doses of morphine can enhance the acute analgesic effect of fentanyl, and this effect is mediated by the delta opioid receptor. This finding is of great therapeutic significance as it suggests a strategy for developing DOP-selective ligands that can enhance the therapeutic index of clinically used MOP drugs.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mydirah Littlepage-Saunders, Michael J. Hochstein, Doris S. Chang, Kari A. Johnson
Summary: Dopamine transmission in the striatum is regulated by various G protein-coupled receptors (GPCRs) that bind neuromodulators, including dopamine itself. These GPCRs can modulate dopamine release by acting on different components of the dopaminergic circuitry and can have distinct effects on behavior and psychoactive drug actions. This review discusses the mechanisms by which GPCRs regulate dopaminergic transmission and their relevance to the effects of psychoactive drugs on physiology and behavior.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Damian Jacenik, Pawel Hikisz, Ellen J. Beswick, Jakub Fichna
Summary: Among the various adhesion G protein-coupled receptors, ADGRF5 stands out with its unique domains in the N-terminal tail that play a critical role in cell-cell and cell-matrix interactions, as well as cell adhesion. Although the biology of ADGRF5 is still not fully understood, accumulating evidence suggests its fundamental importance in both health and disease. Recent studies have highlighted its potential diagnostic value in osteoporosis and cancers, and ongoing research indicates its relevance to other diseases as well. This article provides a comprehensive overview of the current understanding of ADGRF5 in human disease physiology and pathophysiology, emphasizing its potential as a novel therapeutic target in various areas.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Rina Pokhrel, Alexandra L. Morgan, Harley R. Robinson, Martin J. Stone, Simon R. Foster
Summary: G protein-coupled receptor (GPCR) activation triggers complex intracellular signalling networks, which have important implications for receptor biology and drug discovery. Phosphoproteomics has emerged as a powerful tool for investigating these networks and accelerating the discovery of new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Luo, Peng Zhang, Wei Miao, Jie Xiong
Summary: This study provides the first comprehensive genome-wide identification of GPCRs in ciliates, identifying 492 GPCRs in 24 ciliates. GPCRs in ciliates can be assigned to four families, with most belonging to family A. Gene duplication events play a role in the expansion of the GPCR superfamily in ciliates. This study improves our understanding of the evolution and function of GPCRs in ciliates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Francesco Petragnano, Maria Francesca Coppolino, Marco Scarselli, Mario Rossi
Summary: Unstructured regions in functional proteins, specifically the i3 loop and C-terminus in G protein-coupled receptors (GPCRs), have been recognized as crucial elements in GPCR function and regulation. They play critical roles in allosterically regulating GPCR activation, as autoregulators in receptor coupling specificity, and in facilitating receptor stability and interactions with intracellular protein partners.
Article
Pharmacology & Pharmacy
Jyrki P. Kukkonen
Summary: Recent data indicates cooperative effects between identical orthosteric binding sites in a G-protein-coupled receptor dimer. A mathematical model was created to test this concept, showing that even a neutral receptor ligand can allosterically affect agonist binding through the orthosteric binding site.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)