A(3) receptors mediate rapid inflammatory cell influx into the lungs of sensitized guinea-pigs

Background Inhaled adenosine causes bronchoconstriction in asthmatics and m ay modulate inflammatory cell activity. Elevated adenosine levels occur in the lungs after antigen challenge of asthmatics. Objectives The aim of this study was to investigate whether the bronchocons trictor effects of the adenosine derivative, 5'-AMP, were associated with a ltered migration of inflammatory cells into the airways using a sensitized atopic guinea-pig model previously shown to display a bronchoconstrictor re sponse. Comparisons were made with the effects of inhaled antigen. Methods Airway responses of conscious sensitized guinea-pigs to inhalation exposures of 5'-AMP were determined by whole body plethysmography as the ch ange in specific airway conductance (sG(aw)). Influx of leucocytes into the airways was determined by bronchoalveolar lavage (BAL). Results 5'-AMP caused bronchoconstrictor airway responses in sensitized ani mals. Dose-dependent infiltration of inflammatory cells into the lungs occu rred Ih after 5'-AMP exposure. No bronchoconstriction or cell influx was se en in unsensitized guinea-pigs. Exposure to ovalbumin (OA) also caused infl ux of inflammatory cells. Twenty-four hours after an OA exposure, 5'-AMP pr oduced no bronchoconstriction. The P-1-receptor antagonists, 8-PT and 8-SPT , inhibited the 5'-AMP-induced bronchoconstriction, indicating that the bro nchoconstriction seen in sensitized animals is mediated by A(1) or A(2) rec eptors. They had no effect on the cell influx, whereas the A(3) antagonist, MRS-1220, significantly inhibited cellular infiltration, suggesting mediat ion through A(3) receptors. At 24 h after an OA challenge and accompanying the cellular influx. there was airway hyperresponsiveness to the bronchocon striction by histamine. In contrast, no hyper-responsiveness to histamine w as seen 1 h after 3 mM or 24 h after 300 mM 5'-AMP. Conclusions 5'-AMP caused a rapid migration of eosinophils and macrophages into the airways only in sensitized guinea-pigs, and this was blocked by th e A(3) antagonist MRS-1220. This was not associated with bronchial hyper-re activity to histamine.