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

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.

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