Article
Biology
Sebastian Fritzwanker, Falko Nagel, Andrea Kliewer, Viviane Stammer, Stefan Schulz
Summary: Phosphorylation of receptors is unstable during routine immunohistochemical procedures, requiring the use of phosphatase inhibitors for specific GPCR antibodies. We showed that phosphorylation of receptors is highly unstable during routine immunohistochemical procedures, and the use of phosphatase inhibitors is necessary for specific GPCR antibodies. Our findings were confirmed using phosphorylation state-specific MOP and CB1 antibodies.
COMMUNICATIONS BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ferenc Zador, Kornel Kiraly, Nariman Essmat, Mahmoud Al-Khrasani
Summary: This review summarizes recent data on the activation of mu opioid receptor (mu OR) by opioid agonists, including ligand recognition, signal transduction, and structural changes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Kateryna Murlanova, Yan Jouroukhin, Ksenia Novototskaya-Vlasova, Shovgi Huseynov, Olga Pletnikova, Michael J. J. Morales, Yun Guan, Atsushi Kamiya, Dwight E. E. Bergles, David M. M. Dietz, Mikhail V. V. Pletnikov
Summary: The function of mu opioid receptors in astrocytes and their role in reward- and aversion-associated behaviors have been investigated. The knockout of mu opioid receptors in astrocytes did not affect locomotor activity, anxiety, or object recognition in mice exposed to morphine. However, it enhanced locomotor activity and conditioned place aversion during naloxone-precipitated morphine withdrawal, which lasted for up to 6 weeks.
Article
Neurosciences
Peng Huang, Chongguang Chen, Danni Cao, Melody Huang, Lee-Yuan Liu-Chen
Summary: This study demonstrates that agonist-promoted KOR phosphorylation plays important roles in U50,488H-induced tolerance and conditioned place aversion (CPA) in a sex-dependent manner, without affecting acute U50,488H-induced anti-pruritic and hypo-locomotor effects. These results are the first to show sex differences in the effects of GPCR phosphorylation on GPCR-mediated behaviors.
Article
Multidisciplinary Sciences
Shijia Liu, Dong-Il Kim, Tae Gyu Oh, Gerald M. Pao, Jong-Hyun Kim, Richard D. Palmiter, Matthew R. Banghart, Kuo-Fen Lee, Ronald M. Evans, Sung Han
Summary: Neurons expressing the mu-opioid receptor within the lateral parabrachial nucleus play a crucial role in opioid-induced respiratory depression (OIRD). Chemogenetic modulation of these neurons can rescue respiratory rhythms and serve as a potential therapeutic target for treating OIRD in patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Biology
Jennifer M. Kunselman, Achla Gupta, Ivone Gomes, Lakshmi A. Devi, Manojkumar A. Puthenveedu
Summary: The study shows that while multiple physiological agonists can activate the same receptor, it may not necessarily be true redundancy, but rather a way to regulate downstream signaling specificity by controlling the spatiotemporal profile of signaling molecules.
Article
Chemistry, Medicinal
Taryn Bosquez-Berger, Jessica A. Gudorf, Charles P. Kuntz, Jacob A. Desmond, Jonathan P. Schlebach, Michael S. VanNieuwenhze, Alex Straiker
Summary: The US is facing a severe increase in fatal drug overdoses, with synthetic opioids like fentanyl causing 80% of deaths. Naloxone, the only antidote for opiate overdose, struggles against these synthetic opioids. A study has found that (-)-Cannabidiol ((-)-CBD), a candidate negative allosteric modulator (NAM) for the mu opioid receptor, shows potential as a more potent NAM than naloxone. The study suggests that CBD analogs have potential for the development of next-generation antidotes for opioid overdose.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Andrea Vega, Isabel Fredes, Jose O'Brien, Zhouxin Shen, Krisztina otvos, Rashed Abualia, Eva Benkova, Steven P. Briggs, Rodrigo A. Gutierrez
Summary: Nitrate induces genome-wide gene expression changes that affect plant metabolism, physiology, growth, and development. Analysis of the Arabidopsis thaliana root phosphoproteome in response to nitrate treatments identified 176 phosphoproteins with significant changes at 5 or 20 minutes, involving signaling components and transporter activity. The phosphorylation profile of NITRATE TRANSPORTER 1.1 mutant plants indicated its key role in nitrate signaling pathways, with auxin transport highlighted as a mechanism modulated by nitrate at the post-translational level for root growth responses.
Article
Behavioral Sciences
Luke A. Jelen, James M. Stone, Allan H. Young, Mitul A. Mehta
Summary: This article reviews the dysregulation of the opioid system in depression and the potential of pharmacological modulators of mu, delta, and kappa opioid receptors for the treatment of depression. The review presents evidence from animal and clinical studies supporting the dysregulation of the opioid system in depression, the modulation of behavioral processes and brain regions associated with depression by opioids, and the modulation of antidepressant responses by opioids. The review also evaluates clinical trials examining the safety and efficacy of opioidergic agents in depression and explores the involvement of the opioid system in the effects of other treatments, such as ketamine, that exert antidepressant effects through non-opioid actions. Furthermore, the review explores the neurochemical and molecular mechanisms underlying the therapeutic effects of opioid system engagement, providing a rationale for further investigation into this relevant target in depression treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Neurosciences
Nicole E. Ochandarena, Jesse K. Niehaus, Adrien Tassou, Gregory Scherrer
Summary: Opioids are effective analgesics used for pain management, but they have dangerous side effects such as addiction and respiratory depression. The prevalence of opioid abuse and overdose deaths has created an urgent need for safer pain medications and treatments for opioid use disorders. Understanding the cell types and neural circuits responsible for the analgesic and addictive properties of opioids is crucial for research. Single-cell RNA sequencing technology has allowed the identification of MOR-expressing cell types and offers new opportunities for mapping opioid effects onto these cell types.
Article
Chemistry, Multidisciplinary
Ranit Lahmy, Harald Hubner, Maximilian F. Schmidt, Daniel Lachmann, Peter Gmeiner, Burkhard Konig
Summary: This study developed photoswitchable ligands that can activate or deactivate clinically relevant mu-opioid receptors using light, allowing for spatial and temporal control of biological activity in various biological investigations. These ligands, modeled after the known agonist fentanyl, can change geometry upon exposure to light and have different photophysical and biochemical properties, which could be valuable in further studying the functional significance of the mu-opioid receptor.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Neurosciences
Volker Neugebauer, Peyton Presto, Vadim Yakhnitsa, Nico Antenucci, Brianna Mendoza, Guangchen Ji
Summary: Neuroplasticity in cortico-limbic circuits is important in pain persistence and modulation. The amygdala plays a key role in the emotional dimension of pain, and interactions with prefrontal cortical regions change in pain conditions. Other regions in the limbic system are also involved in pain modulation. The corticolimbic system contains opioids and opioid receptors, and their modulatory effects and potential opposing functions are still not fully understood.
Article
Biology
Jordan T. Bateman, Erica S. Levitt
Summary: Opioids inhibit breathing by depressing respiratory nuclei in the pons and medulla. The Kolliker-Fuse (KF) nucleus in the dorsolateral pons, which consists of mu opioid receptor (MOR)-expressing neurons, plays a key role in opioid-induced respiratory depression. MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the preBotzinger complex (preBotC) and rostral ventral respiratory group (rVRG). Glutamatergic projections from dorsolateral pontine neurons to preBotC and rVRG neurons are inhibited by presynaptic opioid receptors. Activation of opioids also hyperpolarizes excitatory preBotC and rVRG neurons, contributing to respiratory depression.
Article
Neurosciences
Josue Jaramillo-Polanco, Cintya Lopez-Lopez, Yang Yu, Emma Neary, Alan Hegron, Meritxell Canals, Nigel W. Bunnett, David E. Reed, Alan E. Lomax, Stephen J. Vanner
Summary: This study found that chronic high-dose opioid exposure leads to opioid-induced hyperalgesia (OIH) in the gastrointestinal tract, which is mediated by DOPr signaling and dependent on receptor endocytosis and protein kinase C signaling.
JOURNAL OF NEUROSCIENCE
(2022)