The Effect of β2 Genetic Polymorphisms on the Brochodilatation Effect of Albuterol ex-Vivo
The Effect of β2 Genetic Polymorphisms on the Brochodilatation Effect of Albuterol ex-Vivo
The role played by ß2AR polymorphisms in determining the bronchial response to ß2AR agonist drugs, has been confirmed by several studies.
The purpose of the present study is to examine possible causal relationships between genetically based alteration in the structure of ß2AR and drug responsiveness. An ex-vivo model (organ bath technique) will be used to investigate association between polymorphisms in the coding region of ß2AR and the response of bronchial rings derived from human lung tissue to the respective agonists (i.e. salbutamol).
In the second part of the study the same bronchial rings will be incubated for 24 hours in a solution containing fixed concentration of albuterol. A second dose response curve for rising concentrations of albuterol will be constructed and a relationship between β2 genetic polymorphisms and the extent of desensitization to albuterol will be investigated.
In addition, through specifically designed receptor binding assay the bronchial tissue will be used to define the affinity (Kd) and expression (Vmax) of the ß2 receptor. These data will enable to enhance our understanding regarding the mechanism responsible for the association noted between ß2AR polymorphism and altered drug effect.
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