Genetic Determinants of the Bronchodilatation Effect of Albuterol ex-Vivo
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
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.