Effects of sensitization on vasoactive intestinal polypeptide-induced relaxation and its concentration and binding in...

We investigated the relaxant effect of vasoactive intestinal polypeptide (VIP) in trachea and lung parenchyma from normal and sensitized guinea-pigs. A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings was used. In intact trachea, concentration-response curves for VIP entering from the mucosal surface (pD2 = 6.61 +/- 0.06) were displaced to the right compared with those for adventitial entry (pD2 = 6.78 +/- 0.04). Epithelium removal produced a leftward shift (approximately 2.8-fold) in the mucosal VIP concentration-response curve. Sensitization did not alter the responsiveness (maximal effect) or sensitivity (pD2 values) of tracheal rings to VIP irrespective of the surface of drug entry and of the absence or presence of epithelium. VIP-induced relaxation of normal and sensitized lung strips was also similar. Sensitization resulted in a significant decrease in tracheal VIP content (from 2.16 +/- 0.07 in normal to 0.60 +/- 0.08 nmol/mg protein in sensitized trachea; P < 0.05; n = 7) whereas the affinity of both high- and low-affinity binding sites for VIP increased as compared to that of normal trachea. Differences were not found in the binding capacities of normal and sensitized trachea. VIP content and binding did not differ in normal and sensitized lung. In conclusion, immunological sensitization produced changes in VIP tracheal content and binding but neither VIP-induced relaxation of isolated airways nor the influence of epithelium in this response was altered.