Review
Biochemistry & Molecular Biology
Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan
Summary: The OPRM1 gene undergoes extensive alternative splicing to produce multiple splice variants with important pharmacological implications for the actions of opioid drugs. These variants can mediate distinct effects of various mu opioids and be targeted for the development of novel analgesics with potent efficacy against multiple types of pain while reducing side effects associated with traditional opiates.
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
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
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
Biochemical Research Methods
Xiang Ma, Desiree A. Johnson, Xinyi Jenny He, Aryanna E. Layden, Shannan P. McClain, Jean C. Yung, Arianna Rizzo, Jordi Bonaventura, Matthew R. Banghart
Summary: CNV-Y-DAMGO allows precise manipulation of mu opioid receptor signaling in behaving mice with high temporal resolution through photopharmacology. Photoactivatable drugs and peptides provide high spatiotemporal precision in quantitative studies of receptor signaling, but are rarely compatible with mammalian behavioral studies. We developed CNV-Y-DAMGO, a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area resulted in an opioid-dependent increase in locomotion within seconds of illumination. These findings highlight the power of in vivo photopharmacology for studying dynamic animal behavior.
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)
Review
Biochemistry & Molecular Biology
Min-Ho Nam, Woojin Won, Kyung-Seok Han, C. Justin Lee
Summary: The mu-opioid receptor (MOR) is crucial for pain relief, reward, and euphoria. Recent research has discovered the presence of MOR in hippocampal astrocytes, shedding light on how astrocytic MOR participates in opioid signaling in the hippocampus. This novel mechanism involving astrocytic MOR plays a key role in hippocampus-dependent conditioned place preference.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
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)
Article
Multidisciplinary Sciences
Ram Kandasamy, Todd M. Hillhouse, Kathryn E. Livingston, Kelsey E. Kochan, Claire Meurice, Shainnel O. Eans, Ming-Hua Li, Andrew D. White, Bernard P. Roques, Jay P. McLaughlin, Susan L. Ingram, Neil T. Burford, Andrew Alt, John R. Traynor
Summary: Positive allosteric modulators (PAMs) of the mu-opioid receptor (MOR) have been suggested as potentially safer analgesics compared to traditional opioid drugs, enhancing the activity of endogenous opioid peptides while reducing side effects. Experimental evidence shows that a specific mu-PAM, BMS-986122, can enhance the potency of endogenous opioid peptides and produce antinociceptive effects in mouse models of acute and inflammatory pain. This innovative approach to pain management may offer a safer alternative to conventional opioid medications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Daniel C. Castro, Corinna S. Oswell, Eric T. Zhang, Christian E. Pedersen, Sean C. Piantadosi, Mark A. Rossi, Avery C. Hunker, Anthony Guglin, Jose A. Moron, Larry S. Zweifel, Garret D. Stuber, Michael R. Bruchas
Summary: The study reveals that mu-opioid peptide receptor regulates reward consumption in mice through a specific pathway from the dorsal raphe to the nucleus accumbens. Inhibition of raphe terminals by MOPR is crucial for determining consummatory response. Activation of enkephalin-containing nucleus accumbens ensembles prior to reward consumption suggests that local enkephalin release is the source of the endogenous MOPR ligand.
Article
Neurosciences
Lihua Sun, Jing Tang, Heidi Liljenback, Aake Honkaniemi, Jenni Virta, Janne Isojarvi, Tomi Karjalainen, Tatu Kantonen, Pirjo Nuutila, Jarmo Hietala, Valtteri Kaasinen, Kari Kalliokoski, Jussi Hirvonen, Harry Scheinin, Semi Helin, Kim Eerola, Eriika Savontaus, Emrah Yatkin, Juha O. Rinne, Anne Roivainen, Lauri Nummenmaa
Summary: The study found that both humans and rats exhibit significant seasonal variations in cerebral MOR availability, primarily associated with seasonal changes in photoperiod. Changes in daylength were shown to influence MOR availability in the brain, impacting behaviors and physiological responses.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Pierre-Eric Lutz, Daniel Almeida, Dominique Filliol, Fabrice Jollant, Brigitte L. Kieffer, Gustavo Turecki
Summary: Research indicates that depression is associated with increased MOR activity, partially explained by a specific increase in expression of the inhibitory alpha G-protein subunit GNAI2. This enhanced endogenous opioidergic tone may help buffer negative affective states in depressed individuals.
NEUROPSYCHOPHARMACOLOGY
(2021)
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
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
Cell Biology
Achla Gupta, Srinivas Gullapalli, Hui Pan, Dinah L. Ramos-Ortolaza, Michael D. Hayward, Malcom J. Low, John E. Pintar, Lakshmi A. Devi, Ivone Gomes
Summary: Activation of mu, delta, and kappa opioid receptors by endogenous opioid peptides plays a crucial role in regulating emotional and physiological responses. Knockout experiments showed that the absence of endogenous opioid peptides significantly affects the levels of Leu-enkephalin, highlighting the importance of proenkephalin as the major source of this peptide. Additionally, the lack of beta-endorphin and/or proenkephalin leads to differential modulation of opioid receptors in a region- and gender-specific manner. These findings demonstrate the importance of endogenous opioid peptides in modulating the expression and activity of opioid receptors in the brain.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Remzi Karayol, Lucian Medrihan, Jennifer L. Warner-Schmidt, Ben W. Fait, Meghana N. Rao, Eva B. Holzner, Paul Greengard, Nathaniel Heintz, Eric F. Schmidt
Summary: The study demonstrates that the loss of functional 5-HT4R specifically from excitatory neurons of the hippocampus leads to AD-like behavioral responses and an increase in anxiety levels, accompanied by an increase in the number of neurons in different regions of the hippocampus. This research highlights the importance of cell type-based approaches in elucidating the complex actions of neuromodulatory systems on neural circuits.
MOLECULAR PSYCHIATRY
(2021)
Review
Neurosciences
Andrea S. Heimann, Camila S. Dale, Francisco S. Guimaraes, Ricardo A. M. Reis, Ami Navon, Michal A. Shmuelov, Vanessa Rioli, Ivone Gomes, Lakshmi L. Devi, Emer S. Ferro
Summary: Hemopressin, derived from hemoglobin alpha-chain, exhibits diverse cannabinoid receptor activities and may have pharmacological effects by interacting with intracellular mitochondrial cannabinoid receptors. The peptide influences physiological processes such as pain, inflammation, appetite, learning, and memory, and shows potential applications in drug delivery systems.
Review
Pharmacology & Pharmacy
Mariana Rae, Mariana Lemos Duarte, Ivone Gomes, Rosana Camarini, Lakshmi A. Devi
Summary: OT and AVP exhibit opposite roles in modulating stress, anxiety, and social behaviors, potentially due to their high sequence homology with their receptors. The crosstalk between these peptides and receptors in vivo remains unclear, but understanding this interaction is essential for elucidating the roles of OT and AVP, as well as for therapeutic targets in treating human disorders.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Reproductive Biology
Sriti Pandey, H. Lakshmi Devi, Irfan Ahmad Bhat, B. Indu, Mukesh Kumar Bharti, Uffaq Shabir, Bilal Ahmad Peer, Vikash Chandra, G. Taru Sharma
Summary: In this study, it was found that P4 supplementation is important for the modulation of adhesion molecules, and co-culturing blastocysts with UECs together affects the expression of adhesion molecules in both blastocysts and UECs.
Article
Neurosciences
Amanda K. Fakira, Lindsay M. Lueptow, Nikita A. Trimbake, Lakshmi A. Devi
Summary: The study reveals a significant but divergent role of GPR83 in different brain regions in regulating anxiety-related behaviors, which is also dependent on sex.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Anesthesiology
Elaine F. Toniolo, Achla Gupta, Adriano C. Franciosi, Ivone Gomes, Lakshmi A. Devi, Camila S. Dale
Summary: The interaction between CB1R and opioid receptors may be targeted for the treatment of diabetic neuropathy. CB1R-MOR and CB1R-DOR complexes are involved in diabetic neuropathy, and the peptide endocannabinoid hemopressin shows potential as a therapeutic for this condition.
Article
Andrology
Abhishek Kumar, Subrata Kumar Ghosh, Rahul Katiyar, Amare Eshetu Gemeda, Rupali Rautela, Amarjeet Bisla, Neeraj Srivastava, Sanjeev Kumar Bhure, Huidrom Lakshmi Devi, Vikash Chandra
Summary: This study investigated the effects of Mito TEMPO and acetovanillone on the freezability of buffalo spermatozoa. The results showed that the addition of these compounds, either individually or in combination, significantly improved post-thaw semen quality.
Article
Pharmacology & Pharmacy
Seshat M. Mack, Ivone Gomes, Amanda K. Fakira, Mariana Lemos Duarte, Achla Gupta, Lloyd Fricker, Lakshmi A. Devi
Summary: PEN is an abundant neuropeptide that activates G protein-coupled receptor 83, playing a role in regulating feeding, reward, and anxiety-related behaviors. Different forms of PEN peptides and procholecystokinin-derived peptides can differentially activate GPR83, showing bias in signal transduction pathways.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Beatriz C. Moraes, Helder Ribeiro-Filho, Allan P. Roldao, Elaine F. Toniolo, Gustavo P. B. Carretero, German G. Sgro, Fernanda A. H. Batista, Damian E. Berardi, Victoria R. S. Oliveira, Rebeka Tomasin, Felipe M. Vieceli, Dimitrius T. Pramio, Alexandre B. Cardoso, Ana C. M. Figueira, Shaker C. Farah, Lakshmi A. Devi, Camila S. Dale, Paulo S. L. de Oliveira, Deborah Schechtman
Summary: Chronic pain is a major health issue, and finding new analgesics is important due to the addictive properties and side effects of opioids. This study investigated mutations in a gene associated with congenital insensitivity to pain with anhidrosis (CIPA) to identify potential drug targets. They developed a cell-permeable phosphopeptide that inhibited a specific signaling pathway and demonstrated pain relief effects.
Article
Reproductive Biology
Lakshmi H. Devi, Shital D. Nagargoje, Shriti Pandey, T. Yasotha, Vikash Chandra, Taru G. Sharma
Summary: This study investigates the impact of buffalo uterine epithelial cells and their conditioned medium on in vitro embryo production. The results show that co-culture of embryos with steroid treated UECs and their CM improves blastocyst and hatching rate.
Article
Neurosciences
Lloyd D. Fricker, Mariana Lemos Duarte, Andrei Jeltyi, Lindsay Lueptow, Amanda K. Fakira, Alexandre K. Tashima, Ute Hochgeschwender, William C. Wetsel, Lakshmi A. Devi
Summary: Carboxypeptidase E (CPE) is not a rate-limiting enzyme in the production of most neuropeptides, contrary to previous claims that small decreases in CPE activity contribute to obesity and other physiological effects.
Article
Optics
R. Reddappa, L. Lakshmi Devi, Ch Basavapoornima, Shobha Rani Depuru, J. Kaewkhao, Wisanu Pecharapa, C. K. Jayasankar
Summary: Di-calcium silicate (Ca2SiO4) phosphors doped with various Ln(3+) ions were prepared using a high temperature solid-state reaction technique. The raw materials were derived from renewable sources instead of non-renewable minerals. The resulting phosphors exhibited strong and characteristic photoluminescence peaks, and their emission characteristics were quantified and found to be better than other phosphors derived from non-renewable minerals. Therefore, Ca2SiO4:Ln(3+) phosphors have the potential to be used in low-cost solid-state lighting devices while utilizing renewable agricultural and food waste materials effectively.
Meeting Abstract
Biochemistry & Molecular Biology
Amanda Fakira, Lindsay Lueptow, Nikita Trimbake, Lakshmi Devi
Article
Biochemistry & Molecular Biology
Lloyd D. Fricker, Alexandre K. Tashima, Amanda K. Fakira, Ute Hochgeschwender, William C. Wetsel, Lakshmi A. Devi
Summary: This study utilized a conditional disruption mouse model of the Cpe gene to identify specific forms of neuropeptides through peptidomics, revealing the specific forms of neuropeptides in cells with disrupted Cpe gene.
CELL CHEMICAL BIOLOGY
(2021)
