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Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults: Discussion

Published in Pulmonary Function

The coding region of the P2AR demonstrates multiple sites of polymorphic variation such as positions 16, 27, and 164. Positions 16 and 27 have been studied extensively both in vitro and in oioo. In vitro, the most impaired polymorphic receptor appears to be due to a threonine to isoleucine change at amino acid 164. However, the heterozygous condition at amino acid 164 occurs in < 5% of the normal population, and the homozygous Ile164 has not been observed in large samples from the general population. In the present study, we chose to examine the effects of exercise on airway function in the Arg16Gly polymorphism, since it is commonly found in the population and also appears to be functionally important. Due to linkage disequilibrium, all homozygous Arg16 subjects in the present study were also homozygous for glutamine at position 27, while position 27 varied (homozygous for glutamine or glutamate, or heterozygous) in the homozygous Gly16 subjects. http://asthma-inhalers-online.com/buy-generic-proventil-online.html

This is in agreement with previous reports’’ regarding the interaction of these polymorphisms. The most notable difference between genotype groups in the present study was the rapid decline in FEF50 in the Arg16 subjects relative to the sustained elevation in FEF50 in the Gly16 subjects during recovery. This potential genotype effect is consistent with previous studies in the peripheral circulation that have suggested that the Gly16 polymorphism is more resistant to vascular desensitization than the Arg16 polymorphism, and in the airways where long-term use of an inhaled P-agonist leads to greater desensitization in the Arg16 genotype when compared to Gly16. Other studies examining P2AR desensitization, however, have been contradictory. In particular, in vitro work by Green et al suggested that when the glycine amino acid is present at position 16, there is enhanced down-regulation of the P2AR. Desensitization of G protein-coupled receptors is a time-dependent process that is initiated on binding to an agonist. There are several mechanisms proposed for desensitization of the P2AR, including the uncoupling of receptors (short-term exposure to a P-agonist) and sequestration of the receptors into the cell that can lead to degradation of the receptor (long-term exposure to a P-agonist).