title: Effects of fostriecin on β2-adrenoceptor-driven responses in human mast cells.
abstract: As part of the intracellular processes leading to mast cell and basophil activation, phosphorylation of key substrates is likely to be important. These processes, mediated by phosphatases, are responsible for regulating phosphorylation. The aim of the present study was to determine effects fostriecin - a selective inhibitor of PP2A (protein phosphatase-2) - on β2-adrenoceptor-driven responses in human mast cells. Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated. Long-term incubation (24 h) of mast cells with fostriecin (10-6M) resulted in a significant (p < 0.001) reduction in the maximal response (from 41.2 [± 3.0] to 29.9 [± 4.2] %) to salbutamol following fostriecin treatment. The results showed that fostriecin pretreatment significantly attenuated the inhibitory effects of salbutamol. Overall, the present study suggested that PP2A has an important role in regulating mast cell β2-adrenoceptors.
authors.affiliation: a Department of Human Vaccines , Razi Serum and Vaccine Research Institute , Karaj , Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Bastan
authors.affiliation: b Department of Immunology , Applied Physiology Research Center, Isfahan University of Medical Sciences , Isfahan , Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Eskandari
authors.affiliation: b Department of Immunology , Applied Physiology Research Center, Isfahan University of Medical Sciences , Isfahan , Iran.
authors.forename: Hamidrez
authors.initials: H
authors.lastname: J Ardakani
authors.affiliation: c Academic Unit of Respiratory Medicine , Medical School, University of Sheffield , Sheffield , UK.
authors.forename: Peter
authors.initials: P
authors.lastname: T Peachell
mesh_terms: D000420:Albuterol / Q000378:metabolism; D001491:Basophils / Q000276:immunology*; D015550:Cell Degranulation; D002478:Cells, Cultured; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation; D011090:Polyenes / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D011090:Polyenes; D011753:Pyrones; D018343:Receptors, Adrenergic, beta-2; D006632:Histamine; D054648:Protein Phosphatase 2; D000420:Albuterol; C040313:fostriecin
keywords: Desensitization; fostriecin; histamine; mast cell