Sci. Signal., 9 November 2010
Taste Receptors Bitter Medicine
John F. Foley
Science Signaling, AAAS, Washington, DC 20005, USA
Obstruction of the airways in people with asthma or other respiratory disorders is due to constriction of airway smooth muscle (ASM). Contraction and relaxation of ASM is controlled by G protein–coupled receptors (GPCRs). GPCRs that promote constriction, such as histamine receptors, stimulate increases in intracellular Ca2+ concentration, whereas GPCRs that promote relaxation, such as the β2-adrenergic receptors (β2ARs), stimulate increases in the intracellular concentration of cyclic adenosine monophosphate (cAMP) and decrease Ca2+ signaling (see commentary by Sanderson and Madison). The group of Deshpande et al. previously screened human ASM cells for the presence of GPCRs that might modulate airway obstruction and found several receptors for bitter tastants (TAS2Rs), as well as their cognate G protein, gustducin. Stimulation of cultured human ASM cells with TAS2R agonists, such as saccharin and chloroquine, resulted in intracellular Ca2+ mobilization, which was comparable to that elicited by stimulation of histamine receptors. However, rather than triggering vasoconstriction, bitter tastants induced the relaxation of intact mouse tracheas. Indeed, the relaxation response to chloroquine was greater than that to the β2AR agonist isoproterenol, although there was no evidence that TAS2Rs had any effect on cAMP abundance. Instead, the authors propose that localized, TAS2R-dependent Ca2+ signaling opens large-conductance Ca2+-activated K+ (BKCa) channels, which cause membrane depolarization and bronchodilation. In a mouse model of asthma, inhalation of the bitter tastant quinine decreased the extent of airway obstruction and was more effective than a β2AR agonist. Together, these data suggest that bitter tastants, either alone or together with current therapeutic agents, may be effective therapies against airway obstruction.
D. A. Deshpande, W. C. H. Wang, E. L. McIlmoyle, K. S. Robinett, R. M. Schillinger, S. S. An, J. S. K. Sham, S. B. Liggett, Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat. Med. 16, 1299–1304 (2010). [PubMed]
M. J. Sanderson, J. M. Madison, Bitter treats for better breathing. Nat. Med. 16, 1190–1191 (2010). [Online Journal]
Citation: J. F. Foley, Bitter Medicine. Sci. Signal. 3, ec340 (2010).
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