Modulation of the bronchomotor effects of chemical mediators by prostaglandin F2 alpha in asthmatic subjects

Abstract

Prostaglandin F2 alpha (PGF2 alpha) is generated by human lung tissue in response to a number of stimuli and is widely viewed as a bronchoconstrictor mediator. We have shown that aerosolized PGF2 alpha in concentrations between 1 and 100 micrograms/ml caused dose-related bronchoconstriction, but that continued stimulation at higher concentrations resulted in a partial return of pulmonary function toward control, suggesting that airways were refractory to further stimulation. To explore the mechanism and specificity of airway refractoriness induced by PGF2 alpha, we examined bronchomotor responses evoked by repeated PGF2 alpha stimulation, repeated histamine stimulation, and PGF2 alpha stimulation followed by histamine. Studies were carried out on 3 separate days in 7 subjects with allergic asthma. For each subject the aerosol concentration of each agonist remained constant throughout the study. Responses were measured as the percent change in FEV1 versus time, and comparisons were made between the first and second agonist challenge of each study day. We found that prior stimulation with PGF2 alpha resulted in diminished airway responsiveness, not only to PGF2 alpha but to histamine as well. In contrast, similar refractoriness could not be induced by repeated histamine stimulation, indicating that the PGF2 alpha-induced decrease in responsiveness was not a nonspecific effect of bronchoconstriction per se. Further, the finding that PGF2 alpha caused a decrease in the response to histamine suggests that diminished airway responsiveness was not due to down-regulation of specific PGF2 alpha receptors. Our findings suggest that in addition to its bronchoconstrictor properties, PGF2 alpha may play a role in the modulation of acute airway responses.