Ionotropic Receptors in Pulmonary Neuroepithelial Bodies (NEB) and their Possible Role in Modulation of Hypoxia Signalling

Abstract

The neuroepithelial bodies (NEB) are specialized pulmonary structures composed of clusters of innervated amine-and peptide-containing cells, widely distributed within airway mucosa of human and animal lung (Lauweryns et al., 1972). NEB cells are preferentially located at or near airway bifurcations, a site ideally suited for sensing changes in airway gas concentration. NEB cells express a membrane-bound 0₂ sensor protein, NADPH oxidase, which appears to function in association with sensitive K⁺ channels (Wang et al., 1996; Fu et al., 1999, 2002). In these specialized receptor cells, hypoxia inhibits Ca²⁺-lependent and Ca²⁺-independent K⁺ channels, leading to an increase in cell firing or a facilitation of membrane depolarization (Youngson et al., 1993). These events are proposed to stimulate neurotransmitter release, which in turn activates second order vagal chemoafferent neurons (Fu et al., 2001). The candidate neurotransmitters involved in chemotransduction of hypoxia stimulus in NEB cells are similar to those proposed for the carotid body glomus cells i.e., serotonin (5-HT), acetycholine (ACh) and ATP (Zhang and Nurse, 2000). Earlier studies reported hypoxia-induced 5-HT release from NEB cells in vivo in neonatal rabbits, and in cultures of NEB cells isolated from