Nedocromil sodium reduces allergen-induced plasma extravasation in the guinea pig nasal mucosa by inhibition of tachykinin release

The effect of topically applied (10 μl) nedocromil sodium (NS) and sodium cromoglycate (CS) on the plasma extravasation induced by local application of ovalbumin (5%, 10 μl) into the respiratory nasal mucosa of sensitized guinea pigs pretreated with the neutral endopeptidase inhibitor, phosphoramidon, was studied. Topical NS (220 nmol, 10 μl) reduced by 57% the Evans blue dye extravasation caused by local application of ovalbumin into the nasal mucosa, whereas CS (220 nmol, 10 μl) was without effect. The tachykinin NK₁ receptor antagonist CP-99994 (2 μmol/kg, i.v.) reduced by 45% the plasma extravasation induced by antigen challenge. The combination of NS and CP-99994 did not increase further the inhibition caused by NS alone. Plasma extravasation evoked by instillation of bradykinin (50 nmol), which causes this response by releasing tachykinins from sensory nerves, was markedly reduced by NS, but not by CS. Plasma extravasation evoked by instillation of substance P, which acts directly on the endothelial cells, was not affected by NS. We conclude that the reduction by NS of the plasma extravasation induced by antigen challenge in the nasal mucosa of sensitized guinea pigs is due to the inhibition of tachykinin release from sensory nerve endings.