title: Direct action and modulating effect of (+)- and (-)-nicotine on ion channels expressed in trigeminal sensory neurons.
abstract: Nicotine sensory perception is generally thought to be mediated by nicotinic acetylcholine (nACh) receptors. However, recent data strongly support the idea that other receptors (e.g., transient receptor potential A1 channel, TRPA1) and other pathways contribute to the detection mechanisms underlying the olfactory and trigeminal cell response to nicotine flavor. This is in accordance with the reported ability of humans to discriminate between (+)- and (-)- nicotine enantiomers. To get a more detailed understanding of the molecular and cellular basis underlying the sensory perception of nicotine, we studied the activity of (+)- and (-)-nicotine on cultured murine trigeminal sensory neurons and on a range of heterologously expressed receptors. The human TRPA1 channel is activated by (-)-nicotine. In this work, we show that (+)-nicotine is also an activator of this channel. Pharmacological experiments using nicotinic acetylcholine receptors and transient receptor potential blockers revealed that trigeminal neurons express one or more unidentified receptors that are sensitive to (+)- and/or (-)-nicotine. Results also indicate that the presence of extracellular calcium ions is required to elicit trigeminal neuron responses to (+)- and (-)-nicotine. Results also show that both (+)-nicotine and (-)-nicotine can block 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses in recombinant expression systems and in cultured trigeminal neurons expressing 5-HT3 receptors. Our investigations broaden the spectra of receptors that are targets for nicotine enantiomers and give new insights into the physiological role of nicotine.
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Benjamin S P
authors: BS
authors: Schreiner
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Ramona
authors: R
authors: Lehmann
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Ulrike
authors: U
authors: Thiel
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Paul M
authors: PM
authors: Ziemba
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Leopoldo R
authors: LR
authors: Beltrán
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany; National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors: Muhammad A
authors: MA
authors: Sherkheli
authors: Philip Morris International R&D, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Philippe
authors: P
authors: Jeanbourquin
authors: Philip Morris International R&D, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Alain
authors: A
authors: Hugi
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Markus
authors: M
authors: Werner
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Günter
authors: G
authors: Gisselmann
authors: Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Hanns
authors: H
authors: Hatt
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009538:Nicotine / Q000737:chemistry / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D009538:Nicotine; D002118:Calcium
keywords: Chemosensation; Human chemoreceptor; Nicotine isomers; Receptor modulation; Recombinant expression; Trigeminal ganglia