NEDOCROMIL SODIUM REDUCES ALLERGEN-INDUCED PLASMA EXTRAVASATION IN THE GUINEA-PIG NASAL-MUCOSA BY INHIBITION OF TACHYKININ RELEASE

The effect of topically applied (10 mu l) nedocromil sodium (NS) and s odium cromoglycate (Cs) on the plasma extravasation induced by local a pplication of ovalbumin (5%, 10 mu l) into the respiratory nasal mucos a of sensitized guinea pigs pretreated with the neutral endopeptidase inhibitor, phosphoramidon, was studied. Topical NS (220 nmol, 10 mu l) reduced by 57% the Evans blue dye extravasation caused by local appli cation of ovalbumin into the nasal mucosa, whereas CS (220 nmol, 10 mu l) was without effect. The tachykinin NK1 receptor antagonist CP-9999 4 (2 mu mol/kg, i.v.) reduced by 45% the plasma extravasation induced by antigen challenge. The combination of NS and CP-99994 did not incre ase further the inhibition caused by NS alone. Plasma extravasation ev oked by instillation of bradykinin (50 nmol), which causes this respon se by releasing tachykinins from sensory nerves, was markedly reduced by NS, but not by Cs. Plasma extravasation evoked by instillation of s ubstance P, which acts directly on the endothelial cells, was not affe cted by NS. We conclude that the reduction by NS of the plasma extrava sation induced by antigen challenge in the nasal mucosa of sensitized guinea pigs is due to the inhibition of tachykinin release from sensor y nerve endings.