Role of protein phosphatases inhibitors on the histamine release and the functional desensitization in human lung mast cells

Abstract

Background: The β2-adrenoceptor agonist, isoprenaline, is an effective inhibitor of histamine release from human lung mast cells (HLMC). Since phosphorylations of the β2-adrenoceptors are probably important in inducing desensitization, we sought to investigate the importance of phosphorylation events by targeting protein phosphatases (PPs) in mast cells. To this end, the effects of the inhibitor of on the functional desensitization of β-adrenoceptor-mediated responses in mast cells were investigated. Materials and Methods: In this study the effects of PP inhibitors on the inhibition of histamine release from HLMC, on β-agonists in mast cells and on desensitization were investigated. Results: Long-term exposure of mast cells to both isoprenaline and salbutamol substantially reduced the extent to which isoprenaline inhibited histamine release. Pretreatments of up to 24 h with inhibitors alone had no effect on immunoglobulin E-mediated histamine release. Shorter (≤4 h) pretreatments had little effect on the activity of isoprenaline and salbutamol to inhibit histamine release from mast cells. Conclusion: Collectively, these data suggest that PP has an important role in regulating mast cell β2-adrenoceptors.

Keywords

• Desensitization
• histamine
• mast cell
• protein phosphatases
• β2 -adrenoceptors