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Background β2-adrenoceptor(β2AR)desensitization is a common problem in clinical practice.β2AR desensitization proceeds by at least such three mechanisms as heterologous desensitization,homologous desensitization and a kind of agonist-induced rapid phosphorylation by a variety of serine/threonine kinases.It is not clear whether there are other mechanisms.This study aimed to investigate potential mechanisms ofβ2AR desensitization.Methods Twenty-four BALB/c(6-8 weeks old)mice were divided into three groups,which is,group A,phosphate buffered saline(PBS)-treated;group B,ovalbumin(OVA)-induced;and group C,salbutamol-treated.Inflammatory cell counts,cytokine concentrations of bronchoalveolar lavage fluid(BALF),pathological sections,total serum IgE,airway responsiveness,membrane receptor numbers and total amount of β2AR were observed.Asthmatic mouse model and β2AR desensitization asthmatic mouse model were established.Groups B and C were selected for two-dimensional gel eleclrophoresis(2DE)analysis so as to find key protein spots related to β2AR desensitization.Results Asthmatic mouse model and β2AR desensitization asthmatic mouse model were verified by inflammatory cell count,cytokine concentration of BALF,serum IgE level,airway hyperreactivity measurement,radioligand receptor binding assay,West blot analysis,and pathologic examination.Then the two groups(groups B and C)were subjected to 2DE.Two key protein spots associated with β2AR desensitization,Rho GDP-dissociation inhibitor 2(RhoGDI2)and peroxiredoxin 5,were found by comparative proteomics(2DE and mass spectrum analysis).Conclusion Oxidative stress and small G protein regulators may play an important role in the process of β2AR desensitization.