Ontogeny of neurokinin-1 receptors in the porcine respiratory system

Abstract

We characterized the ontogeny of NK-1 receptor agonist affinity ( K d) and density ( B max) in membranes from tracheal epithelium, smooth muscle, and lung of pigs aged 1–7 days, 8–21 days, and adult in comparison to contractile responses in vitro. Affinity of [ 125I] Bolton-Hunter substance P ([ 125I]BH-SP) in epithelium and smooth muscle was three- to fourfold lower in young piglets than in adults. The B max of NK-1 sites in epithelium was elevated 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, [ 125I]BH-SP binding was potently inhibited by Gpp(NH)p, in both trachea and lung, implying coupling to G-proteins. Inhibition by Gpp(NH)p was most potent in the adult relative to younger animals, in both tracheal epithelium and smooth muscle. Functional sensitivity to the NK-1 agonists substance P and septide was reduced in neonates, as shown by the higher concentration of agonist required to elicit contractile 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.