Nerve growth factor reduces amiloride‐sensitive Na⁺ transport in human airway epithelial cells through a trkA‐Erk1/2 mediated pathway (660.10)

Abstract

Nerve growth factor (NGF) is over‐expressed in airways of patients with inflammatory lung diseases. Ion transport by the epithelial cells of the lung is responsible for controlling the periciliary liquid layer, and changes in ion transport can accompany disease. To investigate NGF’s effects on airway epithelium, human primary cultured epithelial cells were placed in an Ussing chamber to measure short‐circuit current (Isc). NGF (1 ng/ml), applied apically, reduced Isc (4.5%) and reduced amiloride (apical, 3.5×10‐5 M) ‐sensitive Na+ transport (control, 52%; NGF‐treated, 38%). To investigate whether the NGF receptor, trkA, is responsible for mediating the responses to NGF, cells were incubated with either the tyrosine kinase inhibitor K‐252a (10 nM, apical) or DMSO (0.004 %) in the absence or presence of NGF. K‐252a did not affect Na+transport, but attenuated the NGF‐induced reduction in Na+ transport. To investigate whether trkA activates the Erk1/2 signaling cascade, which results in the down‐regulation of ENaC, cells were incubated with PD‐98059 (30 µM, apical and basolateral) or DMSO (0.06 %) in the absence or presence of NGF. PD‐98059 did not affect Na+ transport, but attenuated the NGF‐induced reduction in Na+ transport. These results indicate that NGF reduces Na+ transport through a trkA‐Erk1/2 mediated signaling pathway. Grant Funding Source: Supported by NIOSH