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 (P(O2) ~155 mmHg; 1 mmHg approximately 133 Pa), most NEB cells did not exhibit detectable secretory activity; however, hypoxia elicited a dose-dependent (P(O2) 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 Ca(2+) channel blocker Cd(2+) (100 microM). Secretion was also largely inhibited by the L-type Ca(2+) channel blocker nifedipine (2 microM), but not by the N-type Ca(2+) channel blocker omega-conotoxin GVIA (1 microM). The 5-HT(3) 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 Ca(2+) channels, as well as by positive feedback activation of 5-HT(3) autoreceptors.
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Division of Pathology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, The Research Institute and University of Toronto, Toronto, Ontario, Canada M5G 1X8.
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Wong
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Cutz
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D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology; D008168:Lung / Q000294:innervation / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology
D015220:Calcium Channels; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D015222:Sodium Channels; D012701:Serotonin