A5043392117- Asthma and respiratory diseases
- Receptor Mechanisms and Signaling
- Inflammatory mediators and NSAID effects
- Neuropeptides and Animal Physiology
- Eicosanoids and Hypertension Pharmacology
- Mast cells and histamine
- Respiratory and Cough-Related Research
- Protein Kinase Regulation and GTPase Signaling
- Antiplatelet Therapy and Cardiovascular Diseases
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- S100 Proteins and Annexins
- Pediatric health and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- Pharmacogenetics and Drug Metabolism
- Estrogen and related hormone effects
- Allergic Rhinitis and Sensitization
- Computational Drug Discovery Methods
- Fatty Acid Research and Health
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Drug-Induced Adverse Reactions
- Nitric Oxide and Endothelin Effects
- Antimicrobial Peptides and Activities
- Cytokine Signaling Pathways and Interactions
University of Milan
2015-2024
International Union of Basic and Clinical Pharmacology
2014
Kyushu University
2006-2011
Brigham and Women's Hospital
2006-2011
Karolinska Institutet
2004-2011
The University of Tokyo
2004-2011
Karolinska University Hospital
2011
Inserm
2006
Université Claude Bernard Lyon 1
2006
GlaxoSmithKline (United States)
2004-2006
Dimeric/oligomeric states of G-protein coupled receptors have been difficult to target. We report here bivalent ligands consisting two identical oxytocin-mimetics that induce a three order magnitude boost in signaling oxytocin (OTRs) vitro and 100- 40-fold gain potency vivo the social behavior mice zebrafish. Through receptor mutagenesis interference experiments with synthetic peptides mimicking transmembrane helices (TMH), we show such superpotent follows from binding dimeric based on...
Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs) are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other conditions. In particular, cysteinyl-LTs exert a variety effects with relevance to aetiology asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion decreased transport and, finally, airway cells (ASMC) proliferation. We used...
The emerging pharmacological target soluble epoxide hydrolase (sEH) is a bifunctional enzyme exhibiting two different catalytic activities that are located in distinct domains. Although the physiological role of C-terminal domain well-investigated, little known about its phosphatase activity, N-terminal sEH (sEH-P). Herein we report discovery and optimization first inhibitor human rat sEH-P applicable vivo. X-ray structure analysis complexed with an provides insights molecular basis...
Both cysteinyl-leukotrienes and extracellular nucleotides mediate inflammatory responses via specific G-protein-coupled receptors, the CysLT P2Y respectively. Since these mediators accumulate at sites of inflammation, cells express both classes their are likely to be crossregulated. We investigated molecular basis desensitization trafficking CysLT1 receptor constitutively transiently expressed in human monocyte/macrophage-like U937 or COS-7 response LTD4 nucleotides. Exposure agonist induced...
Summary Background Montelukast is a potent cysteinyl leukotriene‐1 receptor antagonist possessing some anti‐inflammatory effects although the molecular mechanism of these unknown. In this study, we aimed to investigate effect montelukast on nuclear factor (NF)‐κB‐associated histone acetylation activity in phorbol myristate acetate (PMA)‐differentiated U937 cells. Methods We examined inhibitory TNF‐α‐induced IL‐8 production PMA‐differentiated U‐937 cells were exposed PMA (50 ng/mL) for 48 h...
Multitarget design offers access to bioactive small molecules with potentially superior efficacy and safety. Particularly multifactorial chronic inflammatory diseases demand multiple pharmacological interventions for stable treatment. By minor structural changes, we have developed a close analogue of the cysteinyl-leukotriene receptor antagonist zafirlukast that simultaneously inhibits soluble epoxide hydrolase activates peroxisome proliferator-activated γ. The triple modulator exhibits...
Leukotrienes are important pro-inflammatory lipid mediators derived from the arachidonic acid metabolism. In particular, cysteinyl leukotrienes, namely LTC 4 , LTD and LTE involved in many of principal features asthma, while more recently they have also been implicated cardiovascular diseases. COVID-19 is characterized by an overwhelming state inflammation, sometimes resulting acute respiratory distress syndrome. Furthermore, severe patients present endothelial cell damage a...