Bruno D'Agostino

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It has been documented that beta-adrenergic antagonists can influence platelet aggregation by a mechanism independent of their ability to antagonize beta-adrenoceptors. Nebivolol, a selective beta1-adrenergic receptor antagonist with additional hemodynamic effects, is able to vasodilate human forearm vasculature by acting on the L-arginine/nitric oxide(More)
Sphingosine-1-phosphate (S1P) has been shown to regulate numerous and diverse cell functions, including smooth muscle contraction. Here we assessed the role of S1P/Sphingosine kinase (SPK) pathway in the regulation of bronchial tone. Our objective was to determine, using an integrated pharmacologic and molecular approach, (1) the role of S1P as endogenous(More)
Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and(More)
Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, including chronic cough and exacerbation of asthma. In this study, the potential role of acid-induced tachykinin release was examined in guinea pigs and rabbits, by examining the effects of the tachykinin NK1 and NK3 receptors antagonists (SR 140333(More)
Transforming growth factor-beta1 (TGF-beta1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of(More)
Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that is involved in diverse biological functions. Local administration of S1P causes inflammation coupled to a large eosinophil (EO) recruitment in the rat-paw tissue. The inflammatory response is accompanied by an increase in S1P receptors, namely S1P(1), S1P(2), S1P(3), and by an enhanced expression(More)
BACKGROUND AND PURPOSE 1,4-Benzoquinones are well-known inhibitors of 5-lipoxygenase (5-LOX, the key enzyme in leukotriene biosynthesis), but the molecular mechanisms of 5-LOX inhibition are not completely understood. Here we investigated the molecular mode of action and the pharmacological profile of the novel 1,4-benzoquinone derivative(More)
Endothelin-1 (ET-1) is a potent and efficacious spasmogen of airway smooth muscle. Recent observations suggest that an increased intrapulmonary production of ET-1 may occur in asthma. Our previous study showed that endothelin-1 induced bronchial hyperresponsiveness to inhaled histamine in the rabbit. The aim of this study was to investigate whether the ETA(More)
BACKGROUND AND PURPOSE Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. EXPERIMENTAL APPROACH BALB/c, mast cell-deficient and Nude mice were injected with S1P(More)
We report here the synthesis and preliminary pharmacological characterization of a novel Neurokinin A receptor antagonist. This molecule contains a dehydroalanine residue. It displays a high conformational rigidity and possesses very high activity. Its pharmacological properties as a neurokinin A receptor antagonist were assessed in in vitro experiments on(More)