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Activation of Bitter Taste Receptors Has Distinct Modulatory Effects on Different Lung Afferent Signaling in Rats
Author(s) -
Gu Qihai David,
Gilbert Carolyn,
McLaurin Hugh
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.726.3
Subject(s) - chemistry , trpv1 , agonist , acid sensing ion channel , activator (genetics) , ionotropic effect , receptor , transient receptor potential channel , signal transduction , capsaicin , patch clamp , ion channel , pharmacology , microbiology and biotechnology , glutamate receptor , biochemistry , biology
We have reported recently that activation of bitter taste receptors (T2Rs) in lung nociceptors significantly augments capsaicin‐evoked TRPV1 responses, likely through PLC and PKC intracellular signaling pathway. Using whole‐cell patch‐clamp recordings, the present study was carried out to investigate how T2Rs activation may affect lung sensory neurons responding to different airway stimulations. Three airway irritants that are known to stimulate different pulmonary sensory receptors are selected: zinc, an agonist for TRPA1; low pH or acid, an activator for both acid‐sensing ion channels (ASICs) and TRPV1; and ATP, an agonist for P2X purinoceptors. Our results showed that pretreatment with T2Rs activator chloroquine (0.01, 0.1 and 1 mM, 90 s) concentration‐dependently potentiated zinc (30 μM, 3–16 s)‐evoked TRPA1 currents, and markedly inhibited ATP (0.3 or 1 μM, 4–6 s)‐evoked P2X currents, whereas affected acid (pH 5.5 and pH 6.5, 4–16 s)‐evoked inward currents differently: an inhibition for the slow inactivation ASIC‐like current, and a potentiation for the TRPV1‐like current as well as the fast‐activation and fast‐inactivation ASIC current. Surprisingly, our results also showed that none of the above modulations was completely abolished by the inhibition of PLC, PKC or PKA transduction pathway. In summary, our results demonstrated that T2Rs activation in lung afferents has distinct regulatory effects on various ion channels that are sensitive to different airway irritants. Support or Funding Information Supported by funds from Navicent Health Foundation and MUSM