Ontogeny of neurokinin-1 receptors in the porcine respiratory system

We characterized the ontogeny of NK-1 receptor agonist affinity (K-d) and d ensity (B-max) in membranes from tracheal epithelium, smooth muscle, and lu ng of pigs aged 1-7 days, 8-21 days, and adult in comparison to contractile responses in vitro. Affinity of [I-125] Bolton-Hunter substance P ([I-125] BH-SP) in epithelium and smooth muscle was three- to fourfold lower in youn g piglets than in adults. The B-max of NK-1 sites in epithelium was elevate d by more than twofold at 8-21 days relative to 1-7 days piglets and adults . In the lung, NK-1 density as well as affinity was lower than in trachea, regardless of age. In all three groups, [I-125]BH-SP binding was potently i nhibited by Gpp(NH)p, in both trachea and lung, implying coupling to G-prot eins. Inhibition by Gpp(NH)p was most potent in the adult relative to young er animals, in both tracheal epithelium and smooth muscle. Functional sensi tivity to the NK-1 agonists substance P and septide was reduced in neonates , as shown by the higher concentration of agonist required to elicit contra ctile responses. We conclude that the reduced sensitivity of newborn piglet airways to substance P reflects immaturity of G-protein coupling to NK-1, independent of receptor density. (C) 1999 Elsevier Science Inc. All rights reserved.