Article
Neurosciences
Yasuharu Yamamoto, Keisuke Takahata, Manabu Kubota, Harumasa Takano, Hiroyoshi Takeuchi, Yasuyuki Kimura, Yasunori Sano, Shin Kurose, Hiroshi Ito, Masaru Mimura, Makoto Higuchi
Summary: The study revealed a significant positive correlation between DA synthesis capacity and DA transporter availability in the putamen, but no significant correlation between DA synthesis capacity and D2 receptor availability in the striatum, indicating a relationship between DA synthesis capacity and reuptake, while the total abundance of D2 receptors may not directly participate in the regulatory mechanism.
Article
Pharmacology & Pharmacy
Jose A. Pino, Gabriel Nunez-Vivanco, Gabriela Hidalgo, Miguel Reyes Parada, Habibeh Khoshbouei, Gonzalo E. Torres
Summary: This study reveals that G protein beta gamma subunits can bind to the dopamine transporter (DAT) and activate DAT-mediated dopamine efflux, similar to the mechanism of action of psychostimulants like amphetamine (AMPH). Through a combination of computational biology, mutagenesis, biochemical, and functional assays, the amino acid residues within the 582-596 sequence of the DAT carboxy terminus involved in the DAT-G beta gamma interaction and G beta gamma-induced dopamine efflux were identified. Residues like R588 and F587 within the carboxy terminus of DAT play critical roles in the physical interaction between DAT and G beta gamma, influencing dopamine efflux.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Shin Kurose, Manabu Kubota, Keisuke Takahata, Yasuharu Yamamoto, Hironobu Fujiwara, Yasuyuki Kimura, Hiroshi Ito, Hiroyoshi Takeuchi, Masaru Mimura, Tetsuya Suhara, Makoto Higuchi
Summary: Studies on healthy humans have shown unique structural and functional corticostriatal associations involving D-2 receptors, which appear to be partially independent of the nigrostriatal pathway reflected by striatal DAT.
HUMAN BRAIN MAPPING
(2021)
Article
Behavioral Sciences
Kyna-Anne Conn, Suzy Alexander, Thomas H. J. Burne, James P. Kesby
Summary: This study examines the role of D1 and D2 receptors in learning induced by amphetamine. The results suggest that overall D1 receptor availability is crucial for learning, while modifying D2 receptor function can ameliorate learning deficits in a state of elevated dopamine.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Endocrinology & Metabolism
Jarkko Johansson, Madelene Ericsson, Jan Axelsson, Sara af Bjerken, Ana Virel, Nina Karalija
Summary: Mapping the effects of drugs on the entire brain is crucial for understanding the neural mechanisms behind drug-related behaviors. Using PET, this study investigated the regional and temporal characteristics of amphetamine-induced dopamine release in the brain, revealing distinct responses in different brain regions.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Neurosciences
Vindhya Nawaratne, Sean P. McLaughlin, Felix P. Mayer, Zayna Gichi, Alyssa Mastriano, Lucia Carvelli
Summary: The dopamine 2 receptors (D2R) play an important role in mediating the effects of amphetamine, which primarily rely on the ability of amphetamine to increase extracellular dopamine. This study found that prolonged exposure to amphetamine can decrease or increase endogenous hD2R at the cellular membrane in HEK293 cells. Moreover, the effects of amphetamine on D2R expression may occur independently of dopamine and DAT.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Tao Ke, Ganesh Ambigapathy, Thanh Ton, Archana Dhasarathy, Lucia Carvelli
Summary: This study found that chronic embryonic exposure to amphetamine leads to changes in the expression of the DAT-1 gene in adult C. elegans, which is associated with an enhanced behavioral response to amphetamine in adult animals. Pharmacological and genetic interventions can prevent the long-lasting behavioral effects induced by amphetamine during embryogenesis. These findings are important for understanding how drugs of abuse can predispose to addiction, as the dopaminergic system and epigenetic mechanisms are highly conserved between C. elegans and mammals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Xue-song Liu, Jing Zeng, Yu-xue Yang, Chun-lei Qi, Ting Xiong, Geng-ze Wu, Chun-yu Zeng, Da-xin Wang
Summary: Ischemia-reperfusion (I/R) can cause irreversible damage to the heart, and the regulation of glucose metabolism by GLUT4 and DRD4 is crucial in cardiomyocytes. Activation of DRD4 shows protective effects against I/R injury in cardiomyocytes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Ophthalmology
Furong Huang, Ziheng Shu, Qin Huang, Kaijie Chen, Wenjun Yan, Wenjing Wu, Jinglei Yang, Qiongsi Wang, Fengjiao Wang, Chunlan Zhang, Jia Qu, Xiangtian Zhou
Summary: This study investigates the locations of dopamine D2 receptors (D2Rs) that regulate form-deprivation myopia (FDM) using different transgenic mouse models. The findings suggest that D2Rs located in the retina play a role in the dopaminergic regulation of FDM in mice.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Gui-Long Tian, Chia-Ju Hsieh, Michelle Taylor, Aladdin A. Riad, Robert R. Luedtke, Robert H. Mach
Summary: The difference in the secondary binding site between D2R and D3R has been utilized to design compounds with selectivity for D3R. This study prepared a series of bitopic ligands based on Fallypride to improve the selectivity for D3R using various secondary binding fragments. The results showed that compounds with a small alkyl group containing a heteroatom exhibited improved D3R selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Karolina E. Kolaczynska, Paula Ducret, Daniel Trachsel, Marius C. Hoener, Matthias E. Liechti, Dino Luethi
Summary: This article examines the pharmacological properties of MDA analogs and related amphetamine-based compounds, including monoamine uptake inhibition and release, as well as transporter and receptor binding and activation properties. The study finds that some MDA analogs have similar pharmacological profiles to MDMA, while others have more pronounced dopaminergic activity. Further research on the pharmacokinetics and pharmacodynamics of these drugs is needed to better evaluate their risks and therapeutic potential.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Plant Sciences
Han Zhou, Tao Hou, Zhenhua Gao, Xiujie Guo, Chaoran Wang, Jixia Wang, Yanfang Liu, Xinmiao Liang
Summary: This study isolated eight alkaloids from lotus leaves and evaluated them on dopamine receptors. These alkaloids acted as antagonists for D1 and D2 receptors, with O-nornuciferine being the most potent among the eight on both receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Boeun Lee, Michelle Taylor, Suzy A. Griffin, Tamara McInnis, Nathalie Sumien, Robert H. Mach, Robert R. Luedtke
Summary: The study showed that N-phenylpiperazine analogs can selectively bind to the human D3 dopamine receptor with significant D3 vs. D2 binding selectivity, potentially leading to the development of pharmacotherapeutics for levodopa-induced dyskinesia in patients with Parkinson's disease.
Article
Biochemistry & Molecular Biology
Daiki Masukawa, Satoshi Kitamura, Rei Tajika, Hiraku Uchimura, Masami Arai, Yuuki Takada, Tetsu Arisawa, Momoyo Otaki, Kaori Kanai, Kenta Kobayashi, Tomoyuki Miyazaki, Yoshio Goshima
Summary: Dopamine (DA) is involved in neurological and physiological functions such as motor control. L-3,4-dihydroxyphenylalanine (L-DOPA), traditionally seen as an inert precursor of DA, is now shown to be a neurotransmitter itself.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Felix P. Mayer, Adele Stewart, Randy D. Blakely
Summary: This study shows that aberrant dopamine signaling is associated with various neuropsychiatric disorders, and the dopamine transporter (DAT) and D2-type dopamine autoreceptors (D2AR) play crucial roles in regulating dopamine homeostasis and signaling. The study also reveals a sex-specific capacity of D2AR to regulate DAT in mice with the DAT Val559 variant, leading to different effects on dopamine signaling and behavior in males and females.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Neurosciences
Marquicia R. Pierce, Amita Raj, Katherine M. Betke, L. Nora Zeidan, Heinrich J. G. Matthies, James M. May
JOURNAL OF NEUROSCIENCE RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Morgane Bellot, Segolene Galandrin, Cedric Boularan, Heinrich J. Matthies, Fabien Despas, Colette Denis, Jonathan Javitch, Serge Mazeres, Samra Joke Sanni, Veronique Pons, Marie-Helene Seguelas, Jakob L. Hansen, Atul Pathak, Aurelio Galli, Jean-Michel Senard, Celine Gales
NATURE CHEMICAL BIOLOGY
(2015)
Article
Genetics & Heredity
Peter J. Hamilton, Aparna Shekar, Andrea N. Belovich, Nicole Bibus Christianson, Nicholas G. Campbell, James S. Sutcliffe, Aurelio Galli, Heinrich J. G. Matthies, Kevin Erreger
Article
Medicine, General & Internal
Etienne Cartier, Peter J. Hamilton, Andrea N. Belovich, Aparna Shekar, Nicholas G. Campbell, Christine Saunders, Thorvald F. Andreassen, Ulrik Gether, Jeremy Veenstra-Vanderweele, James S. Sutcliffe, Paula G. Ulery-Reynolds, Kevin Erreger, Heinrich J. G. Matthies, Aurelio Galli
Article
Biochemistry & Molecular Biology
Aparna Shekar, Jenny I. Aguilar, Greta Galli, Nicholas V. Cozzi, Simon D. Brandt, Arnold E. Ruoho, Michael H. Baumann, Heinrich J. G. Matthies, Aurelio Galli
JOURNAL OF CHEMICAL NEUROANATOMY
(2017)
Article
Multidisciplinary Sciences
Nicholas G. Campbell, Aparna Shekar, Jenny I. Aguilar, Dungeng Peng, Vikas Navratna, Dongxue Yang, Alexander N. Morley, Amanda M. Duran, Greta Galli, Brian O'Grady, Ramnarayan Ramachandran, James S. Sutcliffe, Harald H. Sitte, Kevin Erreger, Jens Meiler, Thomas Stockner, Leon M. Bellan, Heinrich J. G. Matthies, Eric Gouaux, Hassane S. Mchaourab, Aurelio Galli
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Medicine, Research & Experimental
Gabriella E. DiCarlo, Jenny I. Aguilar, Heinrich J. G. Matthies, Fiona E. Harrison, Kyle E. Bundschuh, Alyssa West, Parastoo Hashemi, Freja Herborg, Mattias Rickhag, Hao Chen, Ulrik Gether, Mark T. Wallace, Aurelio Galli
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Biochemistry & Molecular Biology
Andrea N. Belovich, Jenny Aguilar, Samuel J. Mabry, Mary H. Cheng, Daniele Zanella, Peter J. Hamilton, Daniel J. Stanislowski, Aparna Shekar, James D. Foster, Ivet Bahar, Heinrich J. G. Matthies, Aurelio Galli
Summary: The study demonstrates the critical role of the interaction between phosphatidylinositol (4, 5)-bisphosphate (PIP2) and DAT N-terminus in AMPH-induced DAT phosphorylation, as well as the electrostatic regulation of DA efflux at R443 in Drosophila. The neutralizing substitution at R443 inhibits the psychomotor actions of AMPH and decreases AMPH-induced DA efflux in isolated fly brains. Notably, the electrostatic interactions of R443 specifically regulate the rewarding properties of AMPH without affecting AMPH aversion.
MOLECULAR PSYCHIATRY
(2021)
Article
Biology
Jenny Aguilar, Mary Hongying Cheng, Josep Font, Alexandra C. Schwartz, Kaitlyn Ledwitch, Amanda Duran, Samuel J. Mabry, Andrea N. Belovich, Yanqi Zhu, Angela M. Carter, Lei Shi, Manju A. Kurian, Cristina Fenollar-Ferrer, Jens Meiler, Renae Monique Ryan, Hassane S. Mchaourab, Ivet Bahar, Heinrich J. G. Matthies, Aurelio Galli
Summary: Parkinson's disease is a progressive neurodegenerative disorder affecting millions worldwide. The study of dopamine transporter deficiency syndrome has provided insights into the molecular mechanisms underlying disease pathology and potential links to Parkinson's disease and Parkinsonism-dystonia. Through molecular modeling and simulations, researchers have identified a specific mutation in the dopamine transporter that disrupts its function, leading to impaired dopamine neurotransmission and associated motor deficits.
Article
Psychiatry
Gabriella E. DiCarlo, Samuel J. Mabry, Xixi Cao, Clara McMillan, Tiffany G. Woynaroski, Fiona E. Harrison, India A. Reddy, Heinrich J. G. Matthies, Charles R. Flynn, Mark T. Wallace, Hui Wu, Aurelio Galli
Summary: The study demonstrates the association between rare variants of the SLC6A3 gene and altered oral microbiota composition, metabolic dysfunction, and other gastrointestinal changes in individuals with ASD.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Medicine, Research & Experimental
Freja Herborg, Kathrine L. Jensen, Sasha Tolstoy, Natascha Arends, Leonie P. Posselt, Aparna Shekar, Jenny Aguilar, Viktor K. Lund, Kevin Erreger, Mattias Rickhag, Matthew D. Lycas, Markus N. Lonsdale, Troels Rahbek-Clemmensen, Andreas T. Sorensen, Amy H. Newman, Annemette Lokkegaard, Ole Kjaerulff, Thomas Werge, Lisbeth B. Moller, Heinrich J. G. Matthies, Aurelio Galli, Lena E. Hjermind, Ulrik Gether
Summary: This study identified the occurrence of the DAT-K619N variant in patients with neuropsychiatric diseases and early-onset neurodegenerative parkinsonism, impacting dopamine transmission. Functional analysis in cell cultures and animal models revealed that DAT-K619N results in impaired dopamine uptake and abnormal behaviors.
Meeting Abstract
Biochemistry & Molecular Biology
Aparna Shekar, Nicholas Campbell, Jenny Aguilar, Dungeng Peng, Kevin Erreger, Heinrich Matthies, James Sutcliffe, Hassane Mchaourab, Aurelio Galli
Meeting Abstract
Biochemistry & Molecular Biology
Jenny Aguilar, Aparna Shekar, Heinrich Matthies, Aurelio Galli
Meeting Abstract
Biochemistry & Molecular Biology
Peter Hamilton, Andrea Belovich, George Khelashvili, Christine Saunders, Kevin Erreger, Jonathan Javitch, Harald Sitte, Harel Weinstein, Heinrich Matthies, Aurelio Galli