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. Aerosolized PGF2.alpha. in concentrations from 1-100 .mu.g/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., bronchomotor responses evoked by repeated PGF2.alpha. stimulation, repeated histamine stimulation and PGF2.alpha. stimulation followed by histamine were examined. 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 [forced expiratory volume in 1 s] vs. time, and comparisons were made between the 1st and 2nd agonist challenge of each study day. Prior stimulation with PGF2.alpha. resulted in diminished airway responsiveness, not only to PGF2.alpha. but to histamine as well. Similar refractoriness could be induced by repeated histamine stimulation, indicating that the PGF2.alpha.-induced decrease in responsiveness was not a nonspecific effect of bronchoconstriction per se. The finding that PGF2.alpha. caused a decreased in the response to histamine suggests that diminished airway responsiveness was not due to down-regulation of specific PGF2.alpha. receptors. In addition to its bronchoconstrictor properties, PGF2.alpha. may play a role in the modulation of acute airway responses.