Article
Biochemistry & Molecular Biology
Richard Agren, Kristoffer Sahlholm
Summary: The study revealed that there is a difference in Ca2+ sensitivity between the two isoforms of dopamine D-2 receptor (D2LR and D2SR), with the desensitization rate of D2SR being influenced by co-expression of GRK2 and beta-arrestin2. The Ca2+ sensitive desensitization of D2SR appears to be mediated via a GRK2 phosphorylation-dependent mechanism.
Article
Biochemistry & Molecular Biology
Dongchen An, Steve Peigneur, Jan Tytgat
Summary: The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. WIN55,212-2, a non-selective agonist of CB1 and CB2, activates CB1 and CB2 at low concentrations and blocks GIRK1/2 at high concentrations.
Article
Neurosciences
L. Duart-Castells, N. Nadal-Gratacos, M. Muralter, B. Puster, X. Berzosa, R. Estrada-Tejedor, M. Niello, S. Bhat, D. Pubill, J. Camarasa, H. H. Sitte, E. Escubedo, R. Lopez-Arnau
Summary: The study highlights the role of amino terminal substitution in the pharmacological profile of novel synthetic cathinones, including their potency in inhibiting dopamine uptake and inducing psychostimulant and rewarding effects in mice. The results demonstrate a significant correlation between predicted binding affinities by molecular docking and affinity constants for human dopamine transporter, indicating the importance of amino substitutions in determining the biological activity of these compounds.
Article
Chemistry, Multidisciplinary
Collin G. Borcik, Isaac R. Eason, Maryam Yekefallah, Reza Amani, Ruixian Han, Boden H. Vanderloop, Benjamin J. Wylie
Summary: Cholesterol oligomers are found in various membrane protein crystal structures, but their biological function is not well understood. This study presents the structural and functional details of a cholesterol dimer that stabilizes the inactivated state of an inward-rectifier potassium channel. The findings provide insights into the role of cholesterol oligomers in regulating channel conductance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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.
Review
Cell Biology
Hua-Qian Yang, Fabio A. Echeverry, Assmaa ElSheikh, Ivan Gando, Sophia Anez Arredondo, Natalie Samper, Timothy Cardozo, Mario Delmar, Show-Ling Shyng, William A. Coetzee
Summary: Sarcolemmal/plasmalemmal ATP-sensitive K+ (K-ATP) channels play crucial roles in various cell types and tissues. Recent studies have highlighted that the surface expression of K-ATP channels is tightly regulated and has significant implications in both health and disease.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
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
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Matthew T. Dickerson, Prasanna K. Dadi, Karolina E. Zaborska, Arya Y. Nakhe, Charles M. Schaub, Jordyn R. Dobson, Nicole M. Wright, Joshua C. Lynch, Claire F. Scott, Logan D. Robinson, David A. Jacobson
Summary: The study demonstrates that G(i/o)-GPCRs hyperpolarize beta-cell membrane potential by activating Na+/K(+)ATPases, leading to decreased insulin secretion. NKAs play a crucial role in this process, regulating electrical excitability, Ca2+ handling, and insulin secretion through a NKA-mediated mechanism.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Ana Simon-Chica, Marbely C. Fernandez, Eike M. Wuelfers, Achim Lother, Ingo Hilgendorf, Gunnar Seemann, Ursula Ravens, Peter Kohl, Franziska Schneider-Warme
Summary: This study characterized the electrophysiological properties of cardiac resident MΦ in mice and explored their potential impact on cardiomyocytes. The research findings provide insights into the involvement of MΦ in cardiac conduction and pave the way for further understanding their role in the heart.
CARDIOVASCULAR RESEARCH
(2022)
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)
Review
Neurosciences
Melinda Hersey, Amanda K. Bacon, Lydia G. Bailey, Mark A. Coggiano, Amy H. Newman, Lorenzo Leggio, Gianluigi Tanda
Summary: The rapid increase in individuals affected by psychostimulant use disorder (PSUD) has highlighted the potential of Modafinil (MOD) as a therapeutic option due to its non-addictive properties, despite its similar mechanism of action to commonly abused psychostimulants on the dopamine transporter (DAT). Clinical and preclinical studies have demonstrated the efficacy of MOD in treating symptoms related to PSUD and other psychiatric disorders involving alterations of brain dopamine systems.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Abigail R. Walker, Camilla B. Larsen, Samit Kundu, Christina Stavrinidis, Sung Hye Kim, Asuka Inoue, David F. Woodward, Yun S. Lee, Roberta Migale, David A. Macntyre, Vasso Terzidou, Francesca Fanelli, Shirin Khanjani, Philip R. Bennet, Aylin C. Hanyaloglu
Summary: Current strategies to manage preterm labor focus on inhibiting uterine contractions, but do not improve neonatal outcomes. This study identifies a mechanism in which activated oxytocin receptor reprograms prostaglandin E2 receptor to promote pro-labor/inflammatory responses during human labor. It suggests a potential therapeutic solution by exploiting the functional associations between these receptors to delay preterm labor.
Article
Biochemistry & Molecular Biology
Beatriz Bueschbell, Prashiela Manga, Erika Penner, Anke C. Schiedel
Summary: Protein-protein interactions between G protein-coupled receptors (GPCRs) can enhance their functionality and expand the range of signaling pathways they regulate. The orphan receptor G protein-coupled receptor 143 (GPR143) has been identified as a new interaction partner for dopamine receptors DRD2 and DRD3. Colocalization and interaction of DRs and GPR143 at intracellular membranes have been observed, with co-expression of GPR143 resulting in decreased DRD2 and DRD3 activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Jace Jones-Tabah
Summary: Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the deterioration of dopaminergic neurons and motor impairment. Although there is no cure for PD, dopamine replacement therapies like L-DOPA can alleviate motor symptoms. However, non-motor symptoms and the progression of neurodegeneration still lack effective treatments. This review focuses on G protein-coupled receptors (GPCRs) as potential targets for treating PD and discusses various therapeutic strategies.
JOURNAL OF MOLECULAR BIOLOGY
(2023)