Article
Pharmacology & Pharmacy
Jia-Jia Zhang, Chang-Geng Song, Miao Wang, Gai-Qin Zhang, Bin Wang, Xi Chen, Peng Lin, Yu-Meng Zhu, Zhi-Chuan Sun, Ya-Zhou Wang, Jian-Li Jiang, Ling Li, Xiang-Min Yang, Zhi-Nan Chen
Summary: In this study, a monoclonal antibody 3A5C7 targeting MOR was developed to alleviate morphine tolerance and dependence by enhancing morphine-induced MOR endocytosis. This provides promising translational value for clinical treatment of morphine tolerance.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)
Article
Neurosciences
Nycole Maza, Dandan Wang, Cody Kowalski, Hannah M. Stoveken, Maria Dao, Omar K. Sial, Andrew C. Giles, Brock Grill, Kirill A. Martemyanov
Summary: Repeated exposure to opioids leads to the development of tolerance, limiting their analgesic effects and increasing the risk of abuse and overdose. This study identified Ptchd1 as a gene involved in regulating opioid tolerance through its effects on receptor trafficking and desensitization. The findings suggest an evolutionarily conserved role for Ptchd1 in protecting against opioid overstimulation.
NATURE NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Lin Li, Jing Chen, Yun-Qing Li
Summary: Neuropathic pain (NP) is a type of pain caused by damage or malfunction of the peripheral or central nervous system. It affects the physical and mental health of 7-10% of the general population. This literature review focuses on the role of downregulation of opioid receptors in the development of NP, particularly from the perspective of dorsal root ganglion, spinal cord, and supraspinal regions. The review also discusses the reasons for the poor efficacy of opioids in NP treatment, including opioid tolerance caused by NP and repeated opioid treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Basile Coutens, Susan L. Ingram
Summary: Opioid receptors are G protein-coupled receptors (GPCRs) that regulate pain, reward, and aversion processing in the brain. They inhibit neurotransmitter release in presynaptic terminals and hyperpolarize neurons in postsynaptic locations. Activation of opioid receptors at the plasma membrane leads to regulatory processes such as phosphorylation and internalization of the receptors. The balance of opioid signaling in circuits expressing pre-and postsynaptic opioid receptors is shifted toward inhibition of presynaptic neurotransmitter release during continuous opioid exposure.
Article
Cell Biology
Ismail Badshah, Maira Anwar, Babar Murtaza, Muhammad Imran Khan
Summary: Drug addiction is a devastating condition that burdens society. The use of drugs like morphine for their analgesic properties often leads to tolerance, dependence, and withdrawal symptoms. This study focuses on exploring the molecular mechanisms and signaling involved in morphine tolerance and dependence, evaluating current therapeutic approaches, and discussing future prospects.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Biology
Seksiri Arttamangkul, Emily J. Platt, James Carroll, David Farrens
Summary: The study found that single cholinergic neurons in the mouse striatum express both MORs and DORs, and through fluorescent labeling and selective activation experiments, it was revealed their mechanisms in regulating cellular electrical activity. The results indicate that the two receptors function independently.
Article
Biology
Damien Jullie, Camila Benitez, Tracy A. Knight, Milos S. Simic, Mark von Zastrow
Summary: This study reveals the cellular mechanism underlying opioid tolerance, mainly through presynaptic tolerance and the endocytosis and recycling process of opioid receptors. The endocytic process of the μ-opioid receptor (MOR) requires phosphorylation mediated by GRK2/3, while the endocytosis of the δ-opioid receptor (DOR) does not require this process. In addition, DOR has a lower efficiency of recycling, resulting in stronger tolerance.
Article
Biochemistry & Molecular Biology
Yusuke Mizobuchi, Kanako Miyano, Sei Manabe, Eiko Uezono, Akane Komatsu, Yui Kuroda, Miki Nonaka, Yoshikazu Matsuoka, Tetsufumi Sato, Yasuhito Uezono, Hiroshi Morimatsu
Summary: This study investigated the effects of ketamine on opioid tolerance and its potential mechanisms. The results showed that ketamine improved acute desensitization and enhanced beta-arrestin recruitment elicited by fentanyl but not by morphine. These effects may involve modulation of GRK-mediated pathways.
Article
Biochemistry & Molecular Biology
Catherine A. Tindall, Kevin Moehlis, Inka Rapoehn, Sebastian Dommel, Veronika Riedl, Michael Schneekoenig, Corinna Hoefling, Steffen Rossner, Jan Stichel, Annette G. Beck-Sickinger, Juliane Weiner, John T. Heiker
Summary: This study reveals the uptake and degradation mechanism of Vaspin in adipocytes, and proposes the Vaspin-LRP1 axis as an important mediator of Vaspin effects not only in adipose tissue but also in other LRP1-expressing cells.
Article
Biochemistry & Molecular Biology
David A. Hernandez-Espinosa, Rocio Alcantara-Hernandez, K. Helivier Solis, J. Adolfo Garcia-Sainz
Summary: By substituting phosphorylation sites with non-phosphorylatable amino acids, the function of the alpha(1B)-adrenergic receptor phosphorylation sites in mediating receptor function was evaluated. The results showed that phosphorylation sites in the IL3 and Ctail domains play a significant role in regulating receptor function and mediating desensitization in response to phorbol ester.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Marc Lopez-Cano, Joan Font, Ester Aso, Kristoffer Sahlholm, Gisela Cabre, Jesus Giraldo, Yves De Koninck, Jordi Hernando, Amadeu Llebaria, Victor Fernandez-Duenas, Francisco Ciruela
Summary: Photopharmacology offers a promising approach to improve the benefit/risk profiles of opioid-based drugs. This study successfully developed a morphine photo-derivative that can be activated by light, providing effective analgesia without the occurrence of tolerance or associated opioid-related side effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Li He, Sarah W. Gooding, Elinor Lewis, Lindsey C. Felth, Anirudh Gaur, Jennifer L. Whistler
Summary: Opioid drugs act by activating the mu-opioid receptor to provide analgesic effects, while potentially leading to side effects such as respiratory depression and tolerance development. Recent studies challenge the prevailing hypothesis that arrestin-3 recruitment contributes to respiratory depression and analgesic tolerance, proposing that future development of safer opioids should target ligands that recruit both G protein and arrestin-3.
NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Immunology
Yi Wang, Cheng-long Zhu, Peng Li, Qiang Liu, Hui-ru Li, Chang-meng Yu, Xiao-ming Deng, Jia-feng Wang
Summary: Sepsis is a life-threatening dysfunction caused by an uncontrolled host response to infection, leading to respiratory dysfunction and acute respiratory distress syndrome (ARDS). Neutrophils, the first line of defense against infection, play a major role in sepsis. However, studies have shown that despite high levels of chemokines at the site of infection, neutrophils cannot migrate properly and instead accumulate in the lungs, causing tissue damage and ARDS. Dysregulation of chemokine receptors, particularly G protein-coupled receptors (GPCRs), is implicated in impaired neutrophil migration. This review summarizes the signaling pathways and mechanisms by which GPCR dysfunction in sepsis leads to impaired neutrophil chemotaxis and proposes potential targets for intervention to improve neutrophil chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Maria Romanova-Michaelides, Zena Hadjivasiliou, Daniel Aguilar-Hidalgo, Dimitris Basagiannis, Carole Seum, Marine Dubois, Frank Juelicher, Marcos Gonzalez-Gaitan
Summary: Research has found that scaling of the Dpp gradient in the Drosophila wing disc is achieved by increasing the contribution of internalized Dpp molecules to Dpp transport, regulated by the extracellular factor Pentagone. This evolutionary mechanism may act on endocytic trafficking to regulate the range and scaling of the gradient, allowing adaptation of shape and pattern to different sizes of organs in different species.