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

Published in Pulmonary Function

Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults: Airway Responses to ExerciseThe focus of our study was to examine the influence of variation in the P2AR gene at codon 16 on the airway responses to exercise in young, healthy adults. We found that the degree of bronchodilation with light- and heavy-intensity exercise was similar between the homozygous Arg16 and Gly16 subjects. However, during the recovery period, the maximal expiratory flow rates in the Arg16 subjects rapidly returned to or fell below baseline values, while the homozygous Gly16 subjects demonstrated a sustained elevation in FEF50 (over pre-exercise values).

A number of previous studies’’’ have demonstrated exercise-related bronchodilation in healthy adults. In the present study, we noted a small rise in FEF50 (3 to 6%) during light exercise with a tendency for the Gly16 subjects to have a greater response. This occurred at a time when catecholamine levels were essentially unchanged from baseline. Thus, it is unlikely that the observed changes with light exercise were due to stimulation of the P2AR unless there are noncatecholamine-mediated pathways that exist, such as a reported interaction between the muscarinic and the P2ARs. The fact that there were only small changes in FEF50 with light exercise suggests that release of vagal tone likely plays little role in the bronchodilation of exercise given this occurred at a time when vagal withdrawal should have been prominent.
With heavier exercise, we noted a gradual rise in FEF50 for both groups over the 9-min workload, increasing 14% and 15% by the end of exercise for the Arg16 and Gly16 subjects, respectively. Previously, we observed similar, or greater, increases in FEF50 with noticeable variability in the changes in airway tone with exercise among healthy subjects, suggesting that genetic variation may play a role. In addition, the degree of bronchodilation appeared to be intensity dependent. In the present study, the marked increase in catecholamines, paralleling the changes in airway function, suggest this is mediated through the P2AR, although in the short duration of catecholamine exposure, there was not a clear genotype related difference.
P2ARs in the lungs are found to be densely distributed over the airway epithelium and alveolar walls.’’ The P2AR is a G protein-coupled receptor that has been shown to lead to bronchodilation in response to a P-agonist. Infusion of epinephrine at levels that are similar to those seen during exercise leads to bronchodilation when compared to placebo.