title: Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study).
abstract: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the ampliﬁcation of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine.
  
  
  
  The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs.
  
  
  
  CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not.
  
  
  
  This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.
authors.affiliation: Unitat d'Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.|Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Munoz-Cano
authors.affiliation: Biochemistry Unit, School of Medicine, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ainsua-Enrich
authors.affiliation: Pharmacology Department, School of Medicine, Universidad de Panamá, Panamá.
authors.forename: I
authors.initials: I
authors.lastname: Torres-Atencio
authors.affiliation: Biochemistry Unit, School of Medicine, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.affiliation: Unitat d'Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.|Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sánchez-Lopez
authors.affiliation: Unitat d'Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.|Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bartra
authors.affiliation: Unitat d'Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.|Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Picado
authors.affiliation: Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain.|Unitat de Rinologia i Clínica de l'Olfacte, Servei d'Oto-rino-laringologia, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Mullol
authors.affiliation: Unitat d'Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain.|Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Valero
mesh_terms: D001381:Azepines / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D017332:Cetirizine / Q000494:pharmacology*; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000187:drug effects / Q000378:metabolism
chemical_list: D001381:Azepines; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D007783:Lactones; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C053321:CV 6209; C052518:WEB 2086; C103639:rupatadine; D003533:Cyproheptadine; C472067:levocetirizine; D017336:Loratadine; C045856:ginkgolide B; D001619:beta-N-Acetylhexosaminidases; C121345:desloratadine; D017332:Cetirizine
keywords: CV6209; Desloratadine; LAD2; Levocetirizine; Mast cell; Platelet-activating factor; Rupatadine.