GENETIC-CONTROL OF INDIRECT AIRWAY RESPONSIVENESS IN THE RAT

Many of the airway responses to endogenous and exogenous stimuli are c aused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoconstri ctor and the plasma protein extravasation response to adenosine and ta chykinins in two highly inbred rat strains, F344 and BDE. BDE-rats hav e a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the di fference in airway responsiveness to adenosine between BDE- and F344-r ats is probably related to a higher number of A3-receptors on the airw ay mast cells of BDE-rats. In contrast, F344-rats have a higher airway responsiveness to tachykinins than BDE-rats. Tachykinins cause bronch oconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats the y cause bronchoconstriction by a direct effect on airway smooth muscle via activation of NK2-receptors. Finally we also observed a differenc e between F344- and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsaicin. In F344-rats but not in BDE-rats mast cell activation a nd the release of 5-hydroxytryptamine is partly responsible for this p lasma protein extravasation.