Hypoxia‐induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit

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Abstract
We examined the effects of hypoxia on the release of serotonin (5-HT) from intact neuroepithelial body cells (NEB), presumed airway chemoreceptors, in rabbit lung slices, using amperometry with carbon fibre microelectrodes. Under normoxia (PO2∼155 mmHg; 1 mmHg ≈133 Pa), most NEB cells did not exhibit detectable secretory activity; however, hypoxia elicited a dose-dependent (PO2 range 95–18 mmHg), tetrodotoxin (TTX)-sensitive stimulation of spike-like exocytotic events, indicative of vesicular amine release. High extracellular K+ (50 mm) induced a secretory response similar to that elicited by severe hypoxia. Exocytosis was stimulated in normoxic NEB cells after exposure to tetraethylammonium (20 mm) or 4-aminopyridine (2 mm). Hypoxia-induced secretion was abolished by the non-specific Ca2+ channel blocker Cd2+ (100 μm). Secretion was also largely inhibited by the L-type Ca2+ channel blocker nifedipine (2 μm), but not by the N-type Ca2+ channel blocker ω-conotoxin GVIA (1 μm). The 5-HT3 receptor blocker ICS 205 930 also inhibited secretion from NEB cells under hypoxia. These results suggest that hypoxia stimulates 5-HT secretion from intact NEBs via inhibition of K+ channels, augmentation of Na+-dependent action potentials and calcium entry through L-type Ca2+ channels, as well as by positive feedback activation of 5-HT3 autoreceptors.