Neuroepithelial bodies in mammalian lung express functional serotonin type 3 receptor

Serotonin (5-HT) type 3 receptor (5-HT3-R) is a ligand-gated ion channel found primarily in the central and peripheral nervous system. We report expression and functional characterization of 5-HT3-R in pulmonary neuroepithelial body (NEB) cells. Using nonisotopic in situ hybridization, we demonstrate expression of 5-HT3-R mRNA in NEB cells in the lungs of different mammals (hamster, rabbit, mouse, and human). Dual immunocytochemistry (for 5-HT and 5-HT3-R) and confocal microscopy localized 5-HT3-R on NEB cell plasma membrane from rabbit. The electrophysiological characteristics of 5-HT3-R in NEB cells were studied in fresh slice's of neonatal hamster lung using the whole cell patch-clamp technique, Application of the 5-HT (5-150 muM) and 5-HT3-R agonist 2-methyl-5-HT (5-150 LM) induced inward currents in a concentration-dependent manner. The 5-HT-induced current was blocked (76.5 +/- .9%) by the specific 5-HT3-R antagonist ICS-205-930 (50 muM), whereas katanserin and p-4-iodo-N(2- [4-(methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinylbenzamide had minimal effects. Forskolin had no effect on desensitization and amplitude of the 5-HT-induced current. The reduction of Ca2+ and Mg2+ in the extracellular solution enhanced the amplitude of the 5-HT-induced current because of slower desensitization. Our studies suggest that 5-HT3-R in NEB cells may function as an autoreceptor and may potentially be involved in modulation of hypoxia signaling.