Neuropeptide release from airways of young and fully-grown rabbits

Nerve growth factor (NGF), a neurotrophin that regulates neuronal development, enhances production of neuropeptides that control airway caliber including substance P (SP). Little is known about the developmental interplay between neurotrophins and neuropeptides. Our goal was to assess release of NGF, SP, and vasoactive intestinal peptide (VIP) from tracheal segments of young (2-week-old) and fully-grown (13-week-old) rabbits, and ascertain location of neuropeptides in airways with mechanical denudation of epithelium and immunohistochemistry. After electrical field stimulation of nerves, bath solutions were collected and immunoassays performed to quantify NGF, SP, and VIP release. There were significant decreases in NGF, SP, and VIP release from airways in 13- versus 2-week-old rabbits. There were also significant decreases in SP and VIP release from denuded versus normal tissues at 2 weeks of age. A similar pattern for SP was seen in 13-week-old rabbits. Immunohistochemistry demonstrated increased neuropeptides in airways from younger rabbits. Although SP was seen in the epithelium and submucosal nerves in the younger group, it was localized to the latter location in fully-grown rabbits. VIP was seen in only submucosal nerves at both ages. Thus, release of NGF, SP, and VIP with neural stimulation decreases in rabbit tracheal segments with age. Decreases in SP with maturation and epithelial denudation appear related in part to decreases in epithelial SP with growth. However, decreases in VIP that occur normally and with epithelial denudation are not explained by location of VIP within the epithelium. The epithelium may be a source of factors that inhibit release of neuropeptides.