A5069079438- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- Computational Drug Discovery Methods
- Nicotinic Acetylcholine Receptors Study
- Cannabis and Cannabinoid Research
- Cellular transport and secretion
- Cardiovascular Function and Risk Factors
- Chemical Synthesis and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Carbon dioxide utilization in catalysis
- Crystallization and Solubility Studies
- Neurobiology and Insect Physiology Research
- bioluminescence and chemiluminescence research
- Cardiomyopathy and Myosin Studies
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Forensic Toxicology and Drug Analysis
- Cardiac, Anesthesia and Surgical Outcomes
- Polymer Foaming and Composites
- X-ray Diffraction in Crystallography
- Phase Equilibria and Thermodynamics
- Cardiac Fibrosis and Remodeling
Drug Discovery Laboratory (Norway)
2025
Universidad del Noreste
2024-2025
Northeastern University
2021-2024
National Institute on Drug Abuse
2013-2021
National Institutes of Health
2014-2021
Centro de Investigación Biomédica en Red
2014-2016
Universitat de Barcelona
2014-2016
Columbia University
1998-2015
University of East Anglia
2014
New York Psychoanalytic Society and Institute
2013
Chemokine receptors constitute an attractive family of drug targets in the frame inflammatory diseases. However, targeting specific chemokine may be complicated by their ability to form dimers or higher order oligomers. Using a combination luminescence complementation and bioluminescence resonance energy transfer assays, we demonstrate for first time existence hetero-oligomeric complexes composed at least three (CCR2, CCR5, CXCR4). We show T cells monocytes that negative binding...
The dopamine D<sub>1</sub> receptor–D<sub>3</sub> receptor (D1R-D3R) heteromer is being considered as a potential therapeutic target for neuropsychiatric disorders. Previous studies suggested that this could be involved in the ability of D3R agonists to potentiate locomotor activation induced by D1R agonists. It has also been postulated its overexpression plays role L-dopa–induced dyskinesia and drug addiction. However, little known about biochemical properties. By combining bioluminescence...
Macrophages are the primary cell type infected with HIV in central nervous system, and infection of these cells is a major component development neuropathogenesis HIV-associated neurocognitive disorders. Within brains drug abusers, macrophages exposed to increased levels dopamine, neurotransmitter that mediates addictive reinforcing effects drugs abuse such as cocaine methamphetamine. In this study we examined dopamine on entry into human macrophages. Exposure during R5 tropic macrophages,...
The G<i>α</i>i/o-coupled dopamine D<sub>2</sub>-like receptor family comprises three subtypes: the D<sub>2</sub> (D2R), with short and long isoform variants (D2SR D2LR), D<sub>3</sub> (D3R), D<sub>4</sub> (D4R), several polymorphic variants. common overlap of norepinephrine innervation expression patterns prompts question a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that can functionally interact D4R. To our knowledge, significant interactions...
It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 (CB1R) localized in glutamatergic nerve terminals mediate the integration endocannabinoid signaling involved modulation striatal excitatory neurotransmission. Previous studies have demonstrated existence A2AR-CB1R artificial cell systems. A dependence A2AR for Gi protein-mediated CB1R was described as one its main biochemical characteristics. However, recent questioned localization functionally...
The development of pharmacotherapeutic treatments psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). atypical DAT inhibitors have received attention due to their promising pharmacological profiles in animal models cocaine and methamphetamine abuse. Herein, we report series modafinil analogues that an inhibitor profile. We extended SAR by chemically manipulating oxidation states...
The gene of a novel prokaryotic member (Tyt1) the neurotransmitter:sodium symporter (NSS) family has been cloned from Fusobacterium nucleatum. In contrast to eukaryotic and some NSSs, which contain 12 transmembrane domains (TMs), Tyt1 contains only 11 TMs, characteristic shared by approximately 70% NSS homologues. Nonetheless upon heterologous expression in an engineered Escherichia coli host, catalyzes robust Na+-dependent, highly selective l-tyrosine transport. Genetic engineering variants...
Both dopamine D3 receptor (D3R) partial agonists and antagonists have been implicated as potential medications for substance use disorders. In contrast to antagonists, may cause fewer side effects since they maintain some dopaminergic tone be less disruptive normal neuronal functions. Here, we report three sets of 4-phenylpiperazine stereoisomers that differ considerably in efficacy: the (R)-enantiomers are antagonists/weak agonists, whereas (S)-enantiomers much more efficacious. To...
The discovery of functionally biased and physiologically beneficial ligands directed toward G-protein coupled receptors (GPCRs) has provided the impetus to design dopamine D2 receptor (D2R) targeted molecules that may be therapeutically advantageous for treatment certain neuropsychiatric or basal ganglia related disorders. Here we describe synthesis a novel series D2R agonists linking unbiased agonist sumanirole with privileged secondary molecular fragments. resulting demonstrate improved...
The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant striatum, while Gs cortex. Yet, little known about their functional distinctions. dopamine D
Signaling bias is the propensity for some agonists to preferentially stimulate G protein-coupled receptor (GPCR) signaling through one intracellular pathway versus another. We previously identified a protein-biased agonist of D2 dopamine (D2R) that results in impaired β-arrestin recruitment. This was predicted arise from unique interactions ligand with hydrophobic pocket at interface second extracellular loop and fifth transmembrane segment D2R. Here, we showed residue Phe189 within this...
The dopamine D4 receptor (D4R) has recently been proposed as an emerging target for treating glioblastoma (GBM). In this article, new piperazine ligands, analogues of the potent and selective D4R lead compounds 9 10, were prepared evaluated their affinity at D2-like subtypes. most promising results obtained by replacing N4-phenyl terminal with a naphthyl group. Indeed, α-naphthyl derivative 15 proved to have four times higher than 9, whereas β-naphthyl compound 16 was about tenfold more 9....
Opium and its derivatives are potent analgesics that can also induce severe side effects, including respiratory depression addiction. Opioids exert their diverse physiological effects through specific membrane-bound receptors. Three major types of opioid receptors have been described, termed delta, kappa, mu. The recent molecular cloning these receptor opens up the possibility to identify ligand-binding domains To kappa delta receptors, we expressed in COS-7 cells cloned mouse chimeric...