title: Activation of bitter taste receptors in pulmonary nociceptors sensitizes TRPV1 channels through the PLC and PKC signaling pathway.
abstract: Bitter taste receptors (T2Rs), a G protein-coupled receptor family capable of detecting numerous bitter-tasting compounds, have recently been shown to be expressed and play diverse roles in many extraoral tissues. Here we report the functional expression of T2Rs in rat pulmonary sensory neurons. In anesthetized spontaneously breathing rats, intratracheal instillation of T2R agonist chloroquine (10 mM, 0.1 ml) significantly augmented chemoreflexes evoked by right-atrial injection of capsaicin, a specific activator for transient receptor potential vanilloid receptor 1 (TRPV1), whereas intravenous infusion of chloroquine failed to significantly affect capsaicin-evoked reflexes. In patch-clamp recordings with isolated rat vagal pulmonary sensory neurons, pretreatment with chloroquine (1-1,000 µM, 90 s) concentration dependently potentiated capsaicin-induced TRPV1-mediated inward currents. Preincubating with diphenitol and denatonium (1 mM, 90 s), two other T2R activators, also enhanced capsaicin currents in these neurons but to a lesser extent. The sensitizing effect of chloroquine was effectively prevented by the phospholipase C inhibitor U73122 (1 µM) or by the protein kinase C inhibitor chelerythrine (10 µM). In summary, our study showed that activation of T2Rs augments capsaicin-evoked TRPV1 responses in rat pulmonary nociceptors through the phospholipase C and protein kinase C signaling pathway.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia gu_q@mercer.edu.
authors.forename: Qihai David
authors.initials: QD
authors.lastname: Gu
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
authors.forename: Deanna S
authors.initials: DS
authors.lastname: Joe
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Gilbert
mesh_terms: D000758:Anesthesia; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013649:Taste / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000098706:Taste Receptors, Type 2
chemical_list: D053119:Benzophenanthridines; D004963:Estrenes; D011760:Pyrrolidinones; D043562:Receptors, G-Protein-Coupled; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000098706:Taste Receptors, Type 2; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002738:Chloroquine; C016299:chelerythrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002211:Capsaicin
keywords: bitter taste; chemoreflex; lung sensory neuron; sensitization; transient receptor potential vanilloid receptor