Neuroepithelial bodies in mammalian lung express functional serotonin type 3 receptor.
Serotonin (5-HT) type 3 receptor (5-HT(3)-R) is a ligand-gated ion channel found primarily in the central and peripheral nervous system. We report expression and functional characterization of 5-HT(3)-R in pulmonary neuroepithelial body (NEB) cells. Using nonisotopic in situ hybridization, we demonstrate expression of 5-HT(3)-R mRNA in NEB cells in the lungs of different mammals (hamster, rabbit, mouse, and human). Dual immunocytochemistry (for 5-HT and 5-HT(3)-R) and confocal microscopy localized 5-HT(3)-R on NEB cell plasma membrane from rabbit. The electrophysiological characteristics of 5-HT(3)-R in NEB cells were studied in fresh slices of neonatal hamster lung using the whole cell patch-clamp technique. Application of the 5-HT (5-150 microM) and 5-HT(3)-R agonist 2-methyl-5-HT (5-150 microM) induced inward currents in a concentration-dependent manner. The 5-HT-induced current was blocked (76.5 +/- 5.9%) by the specific 5-HT(3)-R antagonist ICS-205-930 (50 microM), 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 Ca(2+) and Mg(2+) in the extracellular solution enhanced the amplitude of the 5-HT-induced current because of slower desensitization. Our studies suggest that 5-HT(3)-R in NEB cells may function as an autoreceptor and may potentially be involved in modulation of hypoxia signaling.
Fu
X W
XW
Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada M5G 1X8.
Wang
D
D
Pan
J
J
Farragher
S M
SM
Wong
V
V
Cutz
E
E
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000737:chemistry / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008322:Mammals; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011985:Receptors, Serotonin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D020545:Respiratory Mucosa / Q000294:innervation* / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D005576:Colforsin; D012701:Serotonin; D000077526:Tropisetron; C045918:2-methyl-5-HT; D007650:Ketanserin; D002118:Calcium