A5041483347- Adenosine and Purinergic Signaling
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Olfactory and Sensory Function Studies
- Photochemistry and Electron Transfer Studies
- Neurobiology and Insect Physiology Research
- Click Chemistry and Applications
- Pharmacological Receptor Mechanisms and Effects
- Pain Mechanisms and Treatments
- Metabolism, Diabetes, and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Nerve injury and regeneration
- Electroconvulsive Therapy Studies
- Organic Light-Emitting Diodes Research
- Spectroscopy and Quantum Chemical Studies
- Lipid Membrane Structure and Behavior
- Cardiovascular Issues in Pregnancy
- Advanced Biosensing Techniques and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Cannabis and Cannabinoid Research
- Maternal and fetal healthcare
Universitat de Barcelona
2014-2024
Institut d'Investigació Biomédica de Bellvitge
2014-2024
Bellvitge University Hospital
2024
Departament de Salut
2017-2023
Consejo Superior de Investigaciones Científicas
2008
Universitat de València
1989
Synthesis and characterization of new carbazolyl derivatives with a pendant stable radical the TTM (tris-2,4,6-trichlorophenylmethyl radical) series are reported. The EPR spectra, electrochemical properties, absorption luminescent properties these adducts have been studied. All them show amphotericity being reduced oxidized to their corresponding charged species. luminescence cover red spectral band emission. electron-rich carbazole shows donor−acceptor nature excited state. On other hand,...
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...
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...
Abstract Parkinson’s disease (PD) is a dopaminergic-related pathology in which basal ganglia functioning are altered. It has been postulated that direct receptor-receptor – i.e. dopamine D2 receptor (D2R) and adenosine A2A (A2AR) interaction may be finely regulating this brain area. Accordingly, elucidating whether the prompts changes on these structures could grant valuable information for design of new PD therapies. Here, we first resolved long-standing question concerning D2R-A2AR...
According to the adenosine hypothesis of schizophrenia, classically associated hyperdopaminergic state may be secondary a loss function adenosinergic system. Such hypoadenosinergic might either due reduction extracellular levels or alterations in density A2A receptors (A2ARs) their degree functional heteromerization with dopamine D2 (D2R). In present study, we provide preclinical and clinical evidences for this latter mechanism. Two animal models study schizophrenia endophenotypes, namely...
Caffeine, the most consumed psychoactive substance worldwide, may have beneficial effects on Parkinson's disease (PD) therapy. The mechanism by which caffeine contributes to its antiparkinsonian acting as either an adenosine A2A receptor (A2AR) neutral antagonist or inverse agonist is unresolved. Here we show that A2AR in cell-based functional studies and experimental parkinsonism. Thus, observed triggers a distinct mode, opposite agonist, of receptor's activation switch leading suppression...
Abstract G protein-coupled receptor 37 (GPR37) is an orphan associated to Parkinson’s disease (PD) neuropathology. Here, we identified GPR37 as inhibitor of adenosine A 2A (A R) cell surface expression and function in vivo . In addition, showed that R do oligomerize the striatum. Thus, a close proximity at postsynaptic level striatal synapses was observed by double-labelling post-embedding immunogold detection. Indeed, direct receptor-receptor interaction further substantiated ligation situ...
Background and Purpose Opioid‐based drugs are the gold standard medicines for pain relief. However, tolerance several side effects (i.e. constipation dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic‐mediated adverse effects. Here, we aimed at developing morphine photo‐derivative...
Adenosine A2A receptor (A2AR) antagonists have emerged as complementary non-dopaminergic drugs to alleviate Parkinson's disease (PD) symptomatology. Here, we characterize a novel non-xhantine non-furan A2AR antagonist, PBF509, potential pro-dopaminergic drug for PD management. First, PBF509 was shown be high-affinity ligand at the human A2AR, since it antagonized agonist-mediated cAMP accumulation and impedance responses with KB values of 72.8 ± 17.4 nM 8.2 4.2 nM, respectively. Notably,...
Pain research is mostly based on experimental assays that use animal models, which may allow deciphering the physiopathology of this condition and to propel drug discovery. The formalin nociception test considered one most predictive approaches study acute pain in rodents. This permits monitoring pain-related responses (i.e., itch) caused by a subcutaneous injection an inflammatory agent, namely 2.5% solution, hind paw. After injection, two distinct time periods or phases licking/biting...
Trex2 is a keratinocyte-specific 3'-deoxyribonuclease that participates in the maintenance of skin homeostasis after DNA damage. Here, we show this exonuclease strongly upregulated human psoriasis, hyperproliferative and inflammatory disease. Similarly, imiquimod (IMQ)- Il23-induced mouse psoriasis was associated with substantial upregulation Trex2, which recruited into fragmented chromatin keratinocytes were undergoing impaired proliferation, differentiation, cell death, indicating an...
Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the effects of GUO have been corroborated in cellular models Parkinson's disease (PD), its efficacy as an antiparkinsonian agent has not fully explored PD animal models. Accordingly, we evaluated effectiveness reversing motor impairments several rodent movement disorder models, including catalepsy, tremor, hemiparkinsonism. Our results showed that orally...
The adenosine A2A receptor (A2AR), dopamine D2 (D2R) and metabotropic glutamate type 5 (mGluR5) form A2AR-D2R-mGluR5 heteroreceptor complexes in living cells rat striatal neurons. In the current study, we present experimental data supporting view that A2AR protomer plays a major role inhibitory modulation of density allosteric receptor-receptor interaction within D2R-mGluR5 heteromeric component complex vitro vivo. mGluR5 protomers interact modulate D2R recognition signalling upon forming...
Adenosine receptors (ARs) play many important roles in physiology and have been recognized as potential targets for pain relief. Here, we introduce three photoswitchable adenosine derivatives that function light-dependent agonists ARs confer optical control to these G protein-coupled receptors. One of our compounds, AzoAdenosine-3, was evaluated the classical formalin model pain. The molecule, active dark, not metabolized by deaminase effectively reduced perception a manner. These...
Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active inactive configurations. Here, we developed a photoswitchable adenosine A3 receptor (A3R) agonist that confers optical control on this G protein-coupled through noninvasive topical skin irradiation in an animal model psoriasis. This was achieved by covalently bonding adenosine-5′-methyluronamide moiety to diazocine photochrome, whose singular...
Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning be finely regulated either adenosine A2A receptor (A2AR) or angiotensin type 1 (AT1R) through putative heteromers. Here, we examined whether A2AR AT1R oligomerize in the striatum to synergistically modulate dopaminergic transmission. First, using bioluminescence resonance energy transfer, demonstrated...