Article
Biochemistry & Molecular Biology
Shaili Aggarwal, Mary Hongying Cheng, Joseph M. Salvino, Ivet Bahar, Ole Valente Mortensen
Summary: The dopamine transporter (DAT) plays a critical role in regulating dopamine neurotransmission, with drugs of abuse interacting with DAT to alter its function. A novel allosteric site in DAT has been identified, with the dopaminergic psychostimulant sydnocarb shown to be a ligand of this site. This discovery suggests potential therapeutic implications for allosteric modulation of DAT activity.
Article
Multidisciplinary Sciences
Linda D. Simmler, Yue Li, Lotfi C. Hadjas, Agnes Hiver, Ruud van Zessen, Christian Luscher
Summary: Ketamine does not induce synaptic plasticity in the nucleus accumbens despite eliciting dopamine transients, due to the rapid off-kinetics of the dopamine transients and NMDAR antagonism. However, it supports reinforcement through NMDAR antagonism in GABA neurons of the ventral tegmental area, which is quickly terminated by type-2 dopamine receptors on dopamine neurons.
Article
Biochemistry & Molecular Biology
Ankita Kapoor, Achalla Padmavathi, Sukanya Madhwal, Tina Mukherjee
Summary: In Drosophila, dopamine, a neurotransmitter, plays a critical role in the development and function of blood-progenitor cells in the specialized organ called lymph gland. These cells are able to synthesize dopamine and have the ability to sense dopamine through receptors and transporters. Modulating the expression of dopamine components affects lymph gland growth, and dopamine is involved in regulating the progression of progenitor cells through different phases of the cell cycle. These findings highlight the novel role of dopamine in the myeloid system and its impact on hematopoietic growth and immunity.
Article
Biochemistry & Molecular Biology
Kinga Huminska-Lisowska, Krzysztof Chmielowiec, Aleksandra Stronska-Pluta, Jolanta Chmielowiec, Aleksandra Suchanecka, Jolanta Masiak, Monika Michalowska-Sawczyn, Agnieszka Boron, Pawel Cieszczyk, Anna Grzywacz
Summary: This study investigated the association between methylation in the promoter region of the DAT1 gene and personality traits in athletes. Results showed that athletes scored significantly higher in extraversion and conscientiousness compared to non-athletes. Total methylation and the number of methylated islands in the DAT1 gene were higher in athletes. Correlations were found between methylation levels and extraversion and agreeability traits. This study provides new insights into the biological mechanisms of dopamine release and personality traits in athletes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Plant Sciences
Rainer Hedrich, Ines Kreuzer
Summary: All plants have electrical excitability, but only few can produce a well-defined action potential (AP). The Venus flytrap Dionaea muscipula is able to generate APs with a high firing frequency and speed, allowing it to catch small animals quickly. The captured prey triggers a certain number of APs, which influences the trapping decisions made by the flytrap. The typical Dionaea AP lasts 1 second and consists of five phases, each controlled by specific ion channels, pumps, and carriers.
Article
Multidisciplinary Sciences
Talia Zeppelin, Kasper B. Pedersen, Nils A. Berglund, Xavier Periole, Birgit Schiott
Summary: The human dopamine transporter (hDAT) is a crucial regulator of neurotransmitter dopamine, dysfunction of which is associated with various psychiatric disorders. This study proposed multiple probable dimer conformations through computational simulations and evaluated their relative stability. Results indicated that dimer conformations primarily involve TM9, TM11, and TM12 segments of the protein in the interface.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Cinthia R. Millan, Martina Francis, Nitesh Kumar Khandelwal, Valery F. Thompson, Tarjani M. Thaker, Thomas M. Tomasiak
Summary: The study reveals the important role of the GRD motif in coordinating domain rearrangements in the heterodimeric peptide transporter TmrAB, with disruption of this network leading to different functional consequences and hinting at intrinsic asymmetry in the transporter. These findings suggest a mechanism by which the GRD motifs help coordinate a transition to an outward open conformation, with each half of the transporter playing a different role in the conformational cycle of TmrAB.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Medicine, General & Internal
David Devos, Julien Labreuche, Olivier Rascol, Jean-Christophe Corvol, Alain Duhamel, P. Guyon Delannoy, Werner Poewe, Yaroslau Compta, Nicola Pavese, Evzen Ruzicka, Petr Dusek, Bart Post, Bastiaan R. Bloem, Daniela Berg, Walter Maetzler, Markus Otto, Marie-Odile Habert, Stephane Lehericy, Joaquim Ferreira, Richard Dodel, Christine Tranchant, Alexandre Eusebio, Stephane Thobois, Ana-Raquel Marques, Wassilios G. Meissner, Fabienne Ory-Magne, Uwe Walter, Rob M. A. de Bie, Miguel Gago, Dolores Vilas, Jaime Kulisevsky, Cristina Januario, Miguel V. S. Coelho, Stefanie Behnke, Paul Worth, Klaus Seppi, Thavarak Ouk, Camille Potey, Celine Leclercq, Romain Viard, Gregory Kuchcinski, Renaud Lopes, Jean-Pierre Pruvo, Pascal Pigny, Guillaume Garcon, Ophelie Simonin, Jessica Carpentier, Anne-Sophie Rolland, Dag Nyholm, Christoph Scherfler, Jean-Francois Mangin, Marie Chupin, Regis Bordet, David T. Dexter, Caroline Fradette, Michael Spino, Fernando Tricta, Scott Ayton, Ashley I. Bush, Jean-Christophe Devedjian, James A. Duce, Ioav Cabantchik, Luc Defebvre, Dominique Deplanque, Caroline Moreau
Summary: In a 36-week trial involving participants with early Parkinson's disease who had not received levodopa, treatment with the iron chelator deferiprone led to worse scores in measures of parkinsonism compared to placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hyomin Ahn, Kichul Park, Dongyoung Kim, Sung-Gil Chi, Kee-Hyun Choi, Seo-Jung Han, Chiman Song
Summary: This study examines the pharmacological properties of selective reuptake inhibitors for dopamine, norepinephrine, and serotonin and finds antagonistic effects when they are used in combination. Furthermore, it suggests the presence of a potential secondary inhibitor binding site that affects inhibition.
Article
Multidisciplinary Sciences
Minyoung Oh, Narae Lee, Chanwoo Kim, Hye Joo Son, Changhwan Sung, Seung Jun Oh, Sang Ju Lee, Sun Ju Chung, Chong Sik Lee, Jae Seung Kim
Summary: Dual phase F-18-FP-CIT PET and F-18-FDG PET can aid in the differential diagnosis of degenerative parkinsonism and other parkinsonian disorders, showing a high concordance rate with clinical diagnosis.
SCIENTIFIC REPORTS
(2021)
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)
Review
Neurosciences
Mengfei Bu, Matthew J. Farrer, Habibeh Khoshbouei
Summary: The dopamine transporter (DAT) plays a crucial role in regulating dopamine neurotransmission and is implicated in neurodegenerative diseases like Parkinson's. Surface expression of DAT is dynamically regulated through endocytic trafficking, impacting dopamine signaling. Research shows that dysregulation of DAT trafficking is linked to neurodegenerative diseases.
NPJ PARKINSONS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Ulrik Gether, Harald H. Sitte
Summary: The dopamine transporter utilizes the transmembrane sodium gradient to mediate dopamine reuptake and can form dimers and potentially higher order structures. While the biological importance of this oligomerization is still not fully understood, a study by Sorkina et al. has provided insight into the link between transporter conformation, oligomerization, and endocytosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Neurosciences
Shiyu Wang, Anna I. Neel, Kristen L. Adams, Haiguo Sun, Sara R. Jones, Allyn C. Howlett, Rong Chen
Summary: It has been found that long-term use of atorvastatin reduces the function of dopamine transporter (DAT) in neuroblastoma 2A cells, possibly due to the drug lowering brain cholesterol levels. However, atorvastatin does not have a significant effect on dopamine efflux. This study has important implications for understanding the neurological side effects associated with BBB penetrant statins.
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
Neurosciences
Deborah Rudin, John D. McCorvy, Grant C. Glatfelter, Dino Luethi, Daniel Szoellosi, Tea Ljubisic, Pierce Kavanagh, Geraldine Dowling, Marion Holy, Kathrin Jaentsch, Donna Walther, Simon D. Brandt, Thomas Stockner, Michael H. Baumann, Adam L. Halberstadt, Harald H. Sitte
Summary: APBT isomers are novel psychedelic substances that activate 5-HT2 receptor subtypes and induce head-twitch responses in mice, without causing locomotor stimulation. Replacing the oxygen atom with sulfur enhances their releasing potency at the serotonin transporter, leading to altered in vitro and in vivo profiles. Further research is needed to explore the therapeutic potential of APBT isomers, especially in drug-assisted psychotherapy.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Johanna Irrgeher, Thomas Berger, Anastassiya Tchaikovsky, Cornelius Tschegg, Ghazaleh Gouya, Peter Lechner, Anika Retzmann, Christine Opper, Christa Firbas, Michael Freissmuth, Kerstin Peschel-Credner, Karolina Anderle, Claudia Meisslitzer, Michael Wolzt, Thomas Prohaska
Summary: This article presents an analysis method for Pb isotope pattern deconvolution using enriched Pb-204 as a tracer to monitor trace levels of Pb within the human body. The method overcomes the limitations of using natural lead as a tracer and allows for the calculation of isotope pattern from measured isotope ratios without knowing the quantities of different isotope sources.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Felix P. Mayer, Marco Niello, Daniela Cintulova, Spyridon Sideromenos, Julian Maier, Yang Li, Simon Bulling, Oliver Kudlacek, Klaus Schicker, Hideki Iwamoto, Fei Deng, Jinxia Wan, Marion Holy, Rania Katamish, Walter Sandtner, Yulong Li, Daniela D. Pollak, Randy D. Blakely, Marko D. Mihovilovic, Michael H. Baumann, Harald H. Sitte
Summary: Increasing extracellular levels of serotonin can ameliorate symptoms of depression and anxiety-related disorders. The study found that certain ring-substituted cathinones show preference for the release of serotonin and exert 5-HT-associated effects in behavioral models. These compounds have low abuse liability and potential for adverse events.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Marco Niello, Spyridon Sideromenos, Ralph Gradisch, Ronan O'Shea, Jakob Schwazer, Julian Maier, Nina Kastner, Walter Sandtner, Kathrin Jantsch, Carl R. Lupica, Alexander F. Hoffman, Gert Lubec, Claus J. Loland, Thomas Stockner, Daniela D. Pollak, Michael H. Baumann, Harald H. Sitte
Summary: By using various in vitro, computational, and in vivo approaches, we found that the drug-binding kinetics of S-enantiomers of pyrovalerone analogs at DAT correlate with the time-course of in vivo psychostimulant action in mice. In particular, the slow dissociation (i.e., slow koff) of S-enantiomers of pyrovalerone analogs from DAT can predict their more persistent in vivo effects compared to cocaine and methylphenidate. Overall, our findings highlight the critical importance of drug-binding kinetics at DAT in determining the in vivo profile of effects produced by psychostimulant drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Psychiatry
Felix P. Mayer, Dino Luethi, Lorena B. Areal, Harald H. Sitte
FRONTIERS IN PSYCHIATRY
(2023)
Article
Cell Biology
Thomas J. F. Angenoorth, Julian Maier, Stevan Stankovic, Shreyas Bhat, Sonja Sucic, Michael Freissmuth, Harald H. Sitte, Jae-Won Yang
Summary: Organic cation transporters (OCTs) are membrane proteins that uptake monoamines, cationic drugs and xenobiotics. In this study, the researchers investigated two potentially misfolded variants of organic cation transporter 3 (OCT3) and found that pre-treatment with the chemical chaperone 4-PBA led to increased membrane expression and transport capacity of the misfolded variants. This study provides proof of principle that folding-deficient SLC22 transporter variants, especially OCT3, can be rescued by chaperones.
Article
Biochemistry & Molecular Biology
Michael Freissmuth
Summary: The level of dopamine transporters in the neuronal plasma membrane affects learning and motor coordination in mice. Kearney and colleagues recently showed that dopamine autoreceptors and metabotropic glutamate receptors control the cycling of dopamine transporters in the presynaptic specialization of dopaminergic neurons. These findings have important implications for future studies in neural development and motor learning.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
N. J. Clauss, F. P. Mayer, W. A. Owens, M. Vitela, K. M. Clarke, M. A. Bowman, R. E. Horton, D. Gruendemann, D. Schmid, M. Holy, G. G. Gould, W. Koek, H. H. Sitte, L. C. Daws
Summary: Concurrent cocaine and alcohol use is a dangerous drug combination that increases extracellular monoamines. Ethanol's ability to inhibit monoamine uptake is dependent on the organic cation transporter 3 (OCT3), while cocaine blocks DAT, NET, and SERT. These findings suggest OCT3 as a potential target for therapeutic intervention in ethanol and ethanol/cocaine use disorders.
MOLECULAR PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Michael Eigenschink, Luise Bellach, Sebastian Leonard, Tom Eric Dablander, Julian Maier, Fabian Dablander, Harald H. Sitte
Summary: This study investigates the popularity, usage, and perceived scientific support of Traditional Chinese Medicine (TCM) in Austria. It found that TCM is widely known and used by a substantial proportion of the population, but there is a disparity between the public perception of TCM as scientific and evidence-based studies. It emphasizes the importance of distributing unbiased, science-driven information.
Article
Psychiatry
Jacqueline D. Keighron, Jordi Bonaventura, Yang Li, Jae-Won Yang, Emily M. M. DeMarco, Melinda Hersey, Jianjing Cao, Walter Sandtner, Michael Michaelides, Harald H. H. Sitte, Amy Hauck Newman, Gianluigi Tanda
Summary: Typical and atypical dopamine uptake inhibitors (DUIs) have different effects on behavior, neurochemistry, and addiction potential due to their preference for distinct conformations of the dopamine transporter (DAT) to form ligand-transporter complexes. Cocaine and typical psychostimulants reduce dopamine clearance rate, but only typical DUIs stimulate evoked dopamine release, unrelated to DAT affinity. Pretreatment with a CaMKII alpha inhibitor blunts the stimulatory effects of cocaine on dopamine release, suggesting a role for this kinase in modulating cocaine's effects. Atypical DUIs blunt cocaine's effects, indicating a unique mechanism underlying their potential as medications for psychostimulant use disorder.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Francesca R. Brugnoli, Marion Holy, Marco Niello, Julian Maier, Marcus Hanreich, Mario Menzel, Matthias Haberler, Niklas Zulus, Thomas Pickl, Christa Ivanova, Lisa D. Muiznieks, Benjamin Garlan, Harald H. Sitte
Summary: To address the drawbacks of current techniques in studying the interaction of monoamine transporters, researchers developed an automated microfluidic platform for more accurate and standardized cell-based assays. The platform successfully validated the effects of control compounds such as D-Amphetamine, GBR12909, p-chloroamphetamine, and paroxetine on the two transporters.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Neurosciences
Felix P. Mayer, Marco Niello, Simon Bulling, Yuan-Wei Zhang, Yang Li, Oliver Kudlacek, Marion Holy, Fatemeh Kooti, Walter Sandtner, Gary Rudnick, Diethart Schmid, Harald H. Sitte
Summary: This study provides further insights into the pharmacology of mephedrone at hDAT and hSERT. It was found that mephedrone induces carrier-mediated release via hDAT and hSERT and is sensitive to protein kinase C inhibitor. Additionally, mephedrone displays greater efficacy as a releaser at hSERT than at hDAT, indicating its higher activity at hSERT.
Meeting Abstract
Biophysics
Ralph Gradisch, Daniel Szollosi, Marco Niello, Harald Sitte, Thomas Stockner
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Shreyas Bhat, Marco Niello, Klaus Schicker, Christian Pifl, Harald Sitte, Michael Freissmuth, Walter Sandtner
BIOPHYSICAL JOURNAL
(2022)