A5088909083- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Machine Learning in Bioinformatics
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Photochromic and Fluorescence Chemistry
- Nitric Oxide and Endothelin Effects
- Protein Structure and Dynamics
- Photoreceptor and optogenetics research
- Monoclonal and Polyclonal Antibodies Research
- Pharmacological Effects and Assays
- Pharmacological Receptor Mechanisms and Effects
- Eicosanoids and Hypertension Pharmacology
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- Olfactory and Sensory Function Studies
- Analytical Chemistry and Chromatography
- Adenosine and Purinergic Signaling
- Carcinogens and Genotoxicity Assessment
- Advanced Proteomics Techniques and Applications
- Hormonal Regulation and Hypertension
- Genomics and Rare Diseases
- Pain Mechanisms and Treatments
Universitat Autònoma de Barcelona
2016-2025
Centro de Investigación Biomédica en Red de Salud Mental
2016-2025
Corporació Sanitària Parc Taulí
2018-2025
Centro de Investigación Biomédica en Red
2019-2025
Institute of Research and Innovation Parc Tauli
2018-2025
Instituto de Salud Carlos III
2017-2025
Biomedical Informatics Research Center Antwerp
2024
Research Network (United States)
2024
University of Antwerp
2024
University of South Florida
2023
Exposure of the yeast Saccharomyces cerevisiae to alkaline stress resulted in adaptive changes that involved remodeling gene expression. Recent evidence suggested calcium-activated protein phosphatase calcineurin could play a role signaling. By using an aequorin luminescence reporter, we showed sharp and transient rise cytoplasmic calcium. This increase was largely abolished by addition EGTA medium or cells lacking Mid1 Cch1, components high affinity cell membrane calcium channel. Under...
The sigma-1 (σ(1) ) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there limited understanding of the actions associated with its pharmacological modulation. Indeed, selectivity and properties σ(1) ligands used as tools are unclear demonstration antagonists have efficacy reversing central sensitization-related pain sensitivity still missing.The novel antagonist (S1RA) were first characterized. S1RA was then to investigate effect antagonism receptors on...
Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate role in vascular mesenteric arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments Wistar Kyoto (WKY) SHR were pressurised under passive conditions at a range physiological pressures pressure myography. Confocal microscopy used determine differences quantity organisation intact...
Metabotropic glutamate receptors (mGluRs) are mandatory dimers playing important roles in regulating CNS function. Although assumed to form exclusive homodimers, 16 possible heterodimeric mGluRs have been proposed but their existence native cells remains elusive. Here, we set up two assays specifically identify the pharmacological properties of rat mGlu heterodimers composed mGlu2 and 4 subunits. We used either a heterodimer-specific conformational LRET-based biosensor or system that...
Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions light. We have obtained a series of phenylazopyridines light dependent activity as negative allosteric modulators (NAM) metabotropic glutamate receptor subtype 5 (mGlu5). Here we describe the factors needed achieve an operational molecular photoisomerization and its effective translation into in vitro vivo photoswitching, which includes zebrafish larva motility regulation antinociceptive...
Over the past two decades, opioid epidemic in United States and Canada has evidenced need for a better understanding of molecular mechanisms medications used to fight pain. Morphine fentanyl are widely opiate-mediated analgesia treatment chronic These compounds target μ-opioid receptor (MOR), class A G protein-coupled (GPCR). In light described higher efficacy with respect morphine, we have performed independent μs-length unbiased dynamics (MD) simulations MOR complexes each these ligands,...
E-6837 is a novel, selective and high-affinity 5-HT(6) receptor ligand (pK(i): 9.13) which in vitro demonstrates partial agonism at presumably silent rat full constitutively active human by monitoring the cAMP signaling pathway.The effects of chronic treatment with were determined diet-induced obese (DIO)-rats on changes body weight, food water intake, plasma indices comorbid risk factors, weight regain compound withdrawal. The centrally acting antiobesity drug, sibutramine, was used as...
Type 4 metabotropic glutamate (mGlu4) receptors are emerging targets for the treatment of various disorders. Accordingly, numerous mGlu4-positive allosteric modulators (PAMs) have been identified, some which also display agonist activity. To identify structural bases their action, we explored relationship between binding pockets mGlu4 PAMs with different chemical scaffolds and functional properties. By use innovative biosensors second-messenger assays, show that all enhance action on...
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination induces photochemical reaction prompting active-drug’s release, which effectively controls mGlu5 activity both ectopic expressing systems and striatal primary...
GPCRs play critical roles in cell communication. Although can form heteromers, their role signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs both constitutive homo- and heterodimers. Whereas mGlu2 mGlu4 couple G proteins, protein activation is mediated by heptahelical domain (HD) exclusively mGlu2-4 Such asymmetric transduction results from action of dimeric extracellular...
G-protein-coupled receptors (GPCRs) are important drug targets and a better understanding of their molecular mechanisms would be desirable. The crystallization rate GPCRs has accelerated in recent years as techniques have become more sophisticated, particularly with respect to Class A interacting G-proteins. These developments made it possible for quantitative analysis GPCR geometrical features binding-site conformations, including statistical comparison between active (agonist-bound)...
The present study was designed to analyze the effect of long-term incubation with interleukin-1β (IL-1β) on endothelium-dependent relaxation in rat mesenteric resistance arteries. Vessels were incubated culture medium or without IL-1β (10 ng/ml, 14 h). Changes lumen diameter recorded a pressure myograph. Protein expression, nitrite, and superoxide anion ( \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) ) production evaluated by either Western blot immunofluorescence, Griess reaction, ethidium...
ABSTRACT Potassium homeostasis is crucial for living cells. In the yeast Saccharomyces cerevisiae , uptake of potassium driven by electrochemical gradient generated Pma1 H + -ATPase, and this process represents a major consumer gradient. We considered that any mutation resulting in an alteration could give rise to anomalous sensitivity cationic drug independently its toxicity mechanism. Here, we describe genomewide screen mutants present altered tolerance hygromycin B, spermine,...
The serotonin (5-hydroxytryptamine; 5-HT) 2A receptor is a cell surface class A G protein-coupled that regulates multitude of physiological functions the body and target for antipsychotic drugs. Here we found by means fluorescence resonance energy transfer immunoprecipitation studies 5-HT<sub>2A</sub>-receptor homodimerized in live cells, which linked with its antagonist-dependent fingerprint both binding signaling. Some antagonists, like atypical antipsychotics clozapine risperidone,...
De novo heterozygous mutations in the GNAO1 gene, encoding Gα o subunit of G-proteins, are cause a severe neurodevelopmental disorder, featuring early infantile seizures, profound cognitive dysfunction and, occasionally, movement disorder (early epileptic encephalopathy-17). We report further case this association 20 month-old Spanish girl with neonatal-onset refractory progressive microcephaly, oral-lingual dyskinesia and nearly absent psychomotor development. performed whole-exome...
Lipids are becoming known as essential allosteric modulators of G protein-coupled receptor (GPCRs). However, how they exert their effects on GPCR conformation at the atomic level is still unclear. In light recent experimental data, we have performed several long-timescale molecular dynamics (MD) simulations, totalling 24 μs, to rigorously map modulation and conformational changes in β2 adrenergic (β2AR) that occur a result interactions with three different phospholipids. particular, identify...
Dopamine D₂ receptors (D₂R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development schizophrenia. Pharmacological targeting and modulation equilibrium these receptor homodimers might lead a better understanding critical role played by complexes in physiological pathological conditions. Whereas agonist addition shown prolong D₂R dimer lifetime increase level formation, possible influence antagonists on dimerization...