Influence of beta 2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells.

The phenotypic relevance of allelic variation in the structure of the beta 2-adrenergic receptor (beta 2AR) expressed in lung cells is unknown. In particular, altered responsiveness of the beta 2AR expressed on airway smooth muscle, which are responsible for bronchodilation in the treatment of asthma, may be an important factor in the ultimate physiologic response to agonist. To approach this, we established primary cultures of human airway smooth muscle cells obtained at autopsy and developed a method to determine the beta 2AR genotype at the polymorphic loci of codons 16 and 27, using allele-specific polymerase chain reactions. Radioligand binding studies revealed that these cells expressed approximately 70 fmol/mg of receptor which was exclusively of the beta 2AR subtype. All cell lines obtained (n = 10) exhibited normal agonist binding and receptor-mediated activation of the adenylyl cyclase second messenger pathway. However, distinct differences were found in the response to long-term agonist exposur...