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Genetic control of indirect airway responsiveness in the rat


Professor R. Pauwelk Department of Respiratory Discuses. University Hospital. De Pintelaan 185. B-9000 Ghent. Belgium


Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoamstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains. F344 and BDE. BDE-rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE- and F344-rats is probably related to a higher number of A3-receptors on the airway mast cells of BDE-rats. In contrast. F344-rats have a higher airway responsiveness to lachykinins than BDE-rats. Taehykinins cause bronchoconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats they cause bronchoconstriction by a direct effeet on airway smooth muscle via activation of NK2-receptors. Finally we also observed a difference between F344-and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsuicin. In K344-rats but not in BDE-rats mast cell activation and the release of 5-hydroxytryptamine is partly responsible for this plasma protein extravasation.

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