Article
Biochemistry & Molecular Biology
Agnes Acevedo-Canabal, Travis W. Grim, Cullen L. Schmid, Nina McFague, Edward L. Stahl, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
Summary: Opioid analgesics such as morphine and fentanyl induce hyperactivity in mice through mu-opioid receptor (MOR). This study reveals that noncompetitive agonists at MOR can be used to suppress morphine-induced hyperactivity while enhancing antinociceptive efficacy. Moreover, the intrinsic efficacy measured at the receptor level is not directly proportional to drug efficacy in the locomotor activity assay.
Article
Multidisciplinary Sciences
Brian S. Muntean, Subhi Marwari, Xiaona Li, Douglas C. Sloan, Brian D. Young, James A. Wohlschlegel, Kirill A. Martemyanov
Summary: This study reveals that KCTD proteins, particularly the dominant isoform KCTD5, are major regulators of neuronal cAMP signaling through diverse mechanisms, including modulating Zn2+ influx and G β γ-mediated AC regulation. KCTD5 haploinsufficiency in mice leads to motor deficits that can be reversed by chelating Zn2+.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Trinidad Montero-Melendez, Thomas Boesen, Thomas E. N. Jonassen
Summary: Melanocortin receptors, with their versatile distribution and control over various physiological processes, have become important therapeutic targets for many disorders. Current research focuses on their role in obesity and the treatment of chronic inflammatory and autoimmune diseases. The pro-resolving nature of these drugs allows them to mimic the natural resolution of inflammation, leading to potentially fewer side effects and a balanced response.
SEMINARS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Desye Misganaw
Summary: Dopamine exerts its physiological effects through two subtypes of receptors, which can form heterodimers and higher-order oligomeric complexes, potentially altering signaling and pharmacology. Heteromerization may modify the pharmacological features of individual units, offering a framework for developing promising drugs for specific brain disorders.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Jamie J. Manning, Gabriel Rawcliffe, David B. Finlay, Michelle Glass
Summary: This study investigated the impact of phosphorylation modifications in a specific sequence of the CB1 receptor C-terminus on the translocation of Arrestin-2 and Arrestin-3. The results showed that these modifications partially contributed to the translocation of Arrestin, but complete inhibition was only achieved when all phosphorylation sites were mutated. Additionally, the dissociation of G proteins was also impaired proportionally to the extent of Arrestin translocation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Nathaniel A. K. Glenn, David B. Finlay, Emma R. Carruthers, Kathleen G. Mountjoy, Christopher S. Walker, Natasha L. Grimsey
Summary: The interactions between RAMPs and MRAPs with GPCRs play a significant role in modulating the expression and signaling of these receptors, particularly in cannabinoid receptors CB1, CB2, GPR18, and GPR55. The binding of CB1, CB2, and GPR55 with MRAPs influences their surface expression, possibly through glycosylation and hetero-oligomerization mechanisms, which potentially leads to physiological and disease-related consequences.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Shun Kaneko, Shunsuke Imai, Nobuaki Asao, Yutaka Kofuku, Takumi Ueda, Ichio Shimada
Summary: This study reveals a novel mechanism of GPCR activation and the potential of allosteric modulators to enhance GPCR activity. The use of solution NMR analysis provides insights into the structural changes and equilibrium of GPCRs, shedding light on the rational development of next-generation GPCR-targeting therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
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
Radiology, Nuclear Medicine & Medical Imaging
Ji Hwan Kim, Jonghu Jeon, Young Lee, Seung Min Kim, Miju Cheon, Jun Yup Kim
Summary: This study aimed to understand the development of dysphagia in patients with Parkinson's disease (PD) and identify potential target regions for neuromodulation by analyzing the distribution of dopamine transporter availability in the striatum. The results showed that decreased dopamine transporter availability in specific subregions of the striatum may explain the dysphagia in PD, particularly in the pharyngeal phase.
CLINICAL NUCLEAR MEDICINE
(2023)
Article
Biology
Alexander Soutschek, Susanna C. Weber, Thorsten Kahnt, Boris B. Quednow, Philippe N. Tobler
Summary: The study found that pharmacological manipulations can affect human desires for rewards rather than preferences, with stronger neural connectivity. Opioid receptors impact reward motivation, whereas dopamine receptors do not affect behavior or neural activity.
Review
Cell Biology
Kathryn M. Brewer, Katlyn K. Brewer, Nicholas C. Richardson, Nicolas F. Berbari
Summary: A subset of genetic disorders, known as ciliopathies, are associated with obesity. The mechanisms behind cilia dysfunction and altered energy homeostasis in these syndromes are complex and involve deficits in both development and adult homeostasis. Mutations in cilia-associated genes can also lead to morbid obesity. Cilia play critical roles in energy homeostasis, including food intake regulation, and their dysfunction is linked to obesity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Hospitality, Leisure, Sport & Tourism
Lei Li, Jinye Liang, Cong Zhang, Tiemin Liu, Chao Zhang
Summary: Melanocortin 4 receptor (MC4R) is the most important single-gene cause of human metabolic disorders and has gained significant interest in the research of energy homeostasis and public health. Previous studies primarily focused on the central roles of MC4R, leaving the local expression and behavioral regulation unclear. This article reviews recent studies on the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons, aiming to provide new directions for future research on MC4R signaling.
JOURNAL OF SPORT AND HEALTH SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Kayla E. Kroning, Wenjing Wang
Summary: M-SPOTIT, a genetically encoded fluorescent reporter, can detect MOR activation and leave a green fluorescence mark. It shows high efficiency in detecting opioids in cell cultures and fast detection in neuronal cultures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Monica Patel, Christoph Matti, Natasha L. Grimsey, Daniel F. Legler, Jonathan A. Javitch, David B. Finlay, Michelle Glass
Summary: This study provides novel insights into the regulatory mechanisms of CB2, suggesting that it does not adhere to the classical GPCR regulatory paradigm. The findings indicate that C-terminal aspartic acid residues may play an important role in the activation of beta-arrestin.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Analytical
Thierry Schmidlin, Aijen J. Boender, Christian K. Frese, Albert J. R. Heck, Roger A. H. Adan, A. F. Maarten Altelaar
ANALYTICAL CHEMISTRY
(2015)
Article
Anatomy & Morphology
Kirill Tokarev, Arjen J. Boender, Gala A. E. Classen, Constance Scharff
BRAIN STRUCTURE & FUNCTION
(2016)
Article
Urology & Nephrology
Timo F. W. Soeterik, Paul W. Veenboer, Ralph J. A. Oude-Ophuis, Tycho M. T. W. Lock
INTERNATIONAL JOURNAL OF UROLOGY
(2017)
Article
Neurosciences
Rahul Pandit, Azar Omrani, Mieneke C. M. Luijendijk, Veronne A. J. de Vrind, Andrea J. Van Rozen, Ralph J. A. Oude Ophuis, Keith Garner, Imre Kallo, Alexander Ghanem, Zsolt Liposits, Karl-Klaus Conzelmann, Louk J. M. J. Vanderschuren, Susanne E. la Fleur, Roger A. H. Adan
NEUROPSYCHOPHARMACOLOGY
(2016)
Article
Obstetrics & Gynecology
Iris Muller, Ralph J. A. Oude Ophuis, Frank J. M. Broekmans, Tycho M. T. W. Lock
REPRODUCTIVE BIOMEDICINE ONLINE
(2016)
Article
Endocrinology & Metabolism
M. Merkestein, M. A. van Gestel, E. M. van der Zwaal, M. A. Brans, M. C. Luijendijk, A. J. van Rozen, J. Hendriks, K. M. Garner, A. J. Boender, R. Pandit, R. Adan
INTERNATIONAL JOURNAL OF OBESITY
(2014)
Article
Multidisciplinary Sciences
Rahul Pandit, Esther M. van der Zwaal, Mieneke C. M. Luijendijk, Maike A. D. Brans, Andrea J. van Rozen, Ralph J. A. Oude Ophuis, Louk J. M. J. Vanderschuren, Roger A. H. Adan, Susanne E. la Fleur
Article
Andrology
Joost M. Blok, Caren van Roekel, Ralph J. A. Oude Ophuis, Tycho M. T. W. Lock
Article
Biochemical Research Methods
Laura Alberio, Andrea Locarno, Andrea Saponaro, Edoardo Romano, Valerie Bercier, Shahad Albadri, Federica Simeoni, Silvia Moleri, Silvia Pelucchi, Alessandro Porro, Elena Marcello, Noemi Barsotti, Kerri Kukovetz, Arjen J. Boender, Andrea Contestabile, Shizhen Luo, Aubin Moutal, Yingshi Ji, Giulia Romani, Monica Beltrame, Filippo Del Bene, Monica Di Luca, Rajesh Khanna, Henry M. Colecraft, Massimo Pasqualetti, Gerhard Thiel, Raffaella Tonini, Anna Moroni
Article
Neurosciences
Olga Barca-Mayo, Arjen J. Boender, Andrea Armirotti, Davide De Pietri Tonelli
Article
Behavioral Sciences
Arjen J. Boender, Larry J. Young
HORMONES AND BEHAVIOR
(2020)
Article
Neurosciences
Arjen J. Boender, Leonardo Bontempi, Luca Nava, Yann Pelloux, Raffaella Tonini
Summary: This study reveals that upregulation of EAAT2 in the lateral part of the dorsal striatum is associated with loss of behavioral flexibility, while interfering with this upregulation can preserve behavioral flexibility. Astrocytes play a critical role in regulating striatal functions and shaping behavior.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Amelie M. Borie, Sena Agezo, Parker Lunsford, Arjen J. Boender, Ji-Dong Guo, Hong Zhu, Gordon J. Berman, Larry J. Young, Robert C. Liu
Summary: This study examines the role of oxytocin in the nucleus accumbens during pair bonding in prairie voles. The researchers found that oxytocin's actions change with social experience, regulating the trajectory of social interactions and potentially promoting the maintenance of a pair bond by inhibiting aggressive responses.
Article
Multidisciplinary Sciences
Arjen J. Boender, Marina Boon, Samantha R. Eck, Brandon A. Fricker, Aubrey M. Kelly, Joseph E. LeDoux, Simone C. Motta, Prerana Shrestha, Jack H. Taylor, Brian C. Trainor, Rodrigo Triana-Del Rio, Larry J. Young, H. Elliott Albers
Summary: A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience aims to overcome this issue by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. This study developed a viral-mediated CRISPR/Cas9 strategy that can target the oxytocin receptor (Oxtr) gene in over 80 rodent species, demonstrating the potential of comparative gene editing approaches to improve the translatability of neuroscientific research.
Article
Physiology
Arjen J. Boender, Margriet A. van Gestel, Keith M. Garner, Mieneke C. M. Luijendijk, Roger A. H. Adan
PHYSIOLOGICAL REPORTS
(2014)