Adenosine A(3) receptor-mediated airway microvascular leakage: Role of mast cells and tachykinins

To determine whether adenosine A(3) receptor stimulation produces airway in flammation and, if so, what the mechanism of action is, we studied microvas cular permeability in the rat trachea. After intravenous injection of Evans blue dye, adenosine and various adenosine analogues were given by inhalati on, and the tracheal microvascular permeability was determined by a photome tric measurement of extravasated dye. N-6-2-(4-aminophenyl)-ethyladenosine (APNEA), an adenosine A(3) receptor agonist, dose dependently increased pla sma protein extravasation, whereas adenosine, the A(1)-receptor agonist N-6 -(R-phenylisopropyl)-adenosine, or the A(2)-receptor agonist 5'-N-ethyl-car boxamidoadenosine had no effect. The effect of APNEA was not altered by the adenosine A(1)/A(2) receptor antagonist 8-(p-sulphophenyl)-theophylline, b ut was reduced by depletion of mast cell-derived mediators with compound 48 /80 or pretreatment with the tachykinin NK1 receptor antagonist CP99,994. T hese results suggest that activation of A, receptor specifically increase a irway microvascular permeability probably via mast cell-derived mediators a nd tachykinins.