{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:59:02Z","timestamp":1792619942713,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2010,10,24]],"date-time":"2010-10-24T00:00:00Z","timestamp":1287878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2010,10,24]],"date-time":"2010-10-24T00:00:00Z","timestamp":1287878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2010,11]]},"DOI":"10.1038\/nm.2237","type":"journal-article","created":{"date-parts":[[2010,10,24]],"date-time":"2010-10-24T14:15:23Z","timestamp":1287929723000},"page":"1299-1304","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":601,"title":["Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction"],"prefix":"10.1038","volume":"16","author":[{"given":"Deepak A","family":"Deshpande","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne C H","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L","family":"McIlmoyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S","family":"Robinett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M","family":"Schillinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S K","family":"Sham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B","family":"Liggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,10,24]]},"reference":[{"key":"BFnm2237_CR1","unstructured":"Vignola, A.M., Bonsignore, G., Chanez, P. & Bousquet, J. Fatal Asthma 139\u2013155 (Marcel Dekker, New York, 1998)."},{"key":"BFnm2237_CR2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/rr195","volume":"4","author":"CK Billington","year":"2003","unstructured":"Billington, C.K. & Penn, R.B. Signaling and regulation of G protein\u2013coupled receptors in airway smooth muscle. Respir. Res. 4, 2\u201324 (2003).","journal-title":"Respir. Res."},{"key":"BFnm2237_CR3","doi-asserted-by":"crossref","unstructured":"Green, S.A. & Liggett, S.B. The Genetics of Asthma 67\u201390 (Marcel Dekker, New York, 1996).","DOI":"10.1201\/9781420001723"},{"key":"BFnm2237_CR4","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1258\/0007142001903535","volume":"56","author":"JM Drazen","year":"2000","unstructured":"Drazen, J.M., Silverman, E.K. & Lee, T.H. Heterogeneity of therapeutic responses in asthma. Br. Med. Bull. 56, 1054\u20131070 (2000).","journal-title":"Br. Med. Bull."},{"key":"BFnm2237_CR5","doi-asserted-by":"publisher","first-page":"487","DOI":"10.7326\/0003-4819-130-6-199903160-00005","volume":"130","author":"K Malmstrom","year":"1999","unstructured":"Malmstrom, K. et al. Oral montelukast, inhaled beclomethasone and placebo for chronic asthma. A randomized, controlled trial. Montelukast\/Beclomethasone Study Group. Ann. Intern. Med. 130, 487\u2013495 (1999).","journal-title":"Ann. Intern. Med."},{"key":"BFnm2237_CR6","doi-asserted-by":"publisher","first-page":"5230","DOI":"10.1073\/pnas.0801319105","volume":"105","author":"R Einstein","year":"2008","unstructured":"Einstein, R. et al. Alternative splicing of the G protein\u2013coupled receptor superfamily in human airway smooth muscle diversifies the complement of receptors. Proc. Natl. Acad. Sci. USA 105, 5230\u20135235 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm2237_CR7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1165\/rcmb.2008-0266OC","volume":"41","author":"AM Misior","year":"2009","unstructured":"Misior, A.M. et al. Glucocorticoid- and protein kinase A\u2013dependent transcriptome regulation in airway smooth muscle. Am. J. Respir. Cell Mol. Biol. 41, 24\u201339 (2009).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"BFnm2237_CR8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1152\/physiolgenomics.00134.2006","volume":"29","author":"Y Boss\u00e9","year":"2007","unstructured":"Boss\u00e9, Y., Maghni, K. & Hudson, T.J. 1\u03b1,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility and remodeling processes. Physiol. Genomics 29, 161\u2013168 (2007).","journal-title":"Physiol. Genomics"},{"key":"BFnm2237_CR9","first-page":"37","volume":"154","author":"W Meyerhof","year":"2005","unstructured":"Meyerhof, W. Elucidation of mammalian bitter taste. Rev. Physiol. Biochem. Pharmacol. 154, 37\u201372 (2005).","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"BFnm2237_CR10","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/chemse\/bjp092","volume":"35","author":"W Meyerhof","year":"2010","unstructured":"Meyerhof, W. et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 35, 157\u2013170 (2010).","journal-title":"Chem. Senses"},{"key":"BFnm2237_CR11","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S0092-8674(00)80706-0","volume":"100","author":"J Chandrashekar","year":"2000","unstructured":"Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100, 703\u2013711 (2000).","journal-title":"Cell"},{"key":"BFnm2237_CR12","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0092-8674(00)80705-9","volume":"100","author":"E Adler","year":"2000","unstructured":"Adler, E. et al. A novel family of mammalian taste receptors. Cell 100, 693\u2013702 (2000).","journal-title":"Cell"},{"key":"BFnm2237_CR13","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nature05401","volume":"444","author":"J Chandrashekar","year":"2006","unstructured":"Chandrashekar, J., Hoon, M.A., Ryba, N.J. & Zuker, C.S. The receptors and cells for mammalian taste. Nature 444, 288\u2013294 (2006).","journal-title":"Nature"},{"issue":"Suppl 4","key":"BFnm2237_CR14","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1289\/ehp.00108s4697","volume":"108","author":"LJ Lombardo","year":"2000","unstructured":"Lombardo, L.J. & Balmes, J.R. Occupational asthma: a review. Environ. Health Perspect. 108 Suppl 4, 697\u2013704 (2000).","journal-title":"Environ. Health Perspect."},{"key":"BFnm2237_CR15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1165\/rcmb.2005-0453OC","volume":"35","author":"SS An","year":"2006","unstructured":"An, S.S., Fabry, B., Trepat, X., Wang, N. & Fredberg, J.J. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness? Am. J. Respir. Cell Mol. Biol. 35, 55\u201364 (2006).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"BFnm2237_CR16","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1113\/expphysiol.2008.042432","volume":"93","author":"G Martin","year":"2008","unstructured":"Martin, G. et al. Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cells. Exp. Physiol. 93, 908\u2013918 (2008).","journal-title":"Exp. Physiol."},{"key":"BFnm2237_CR17","doi-asserted-by":"publisher","first-page":"L1037","DOI":"10.1152\/ajplung.00145.2007","volume":"293","author":"C Morin","year":"2007","unstructured":"Morin, C., Sirois, M., Echave, V., Gomes, M.M. & Rousseau, E. Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L1037\u2013L1044 (2007).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm2237_CR18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1146\/annurev.ph.58.030196.000555","volume":"58","author":"MI Kotlikoff","year":"1996","unstructured":"Kotlikoff, M.I. & Kamm, K.E. Molecular mechanisms of \u03b2-adrenergic relaxation of airway smooth muscle. Annu. Rev. Physiol. 58, 115\u2013141 (1996).","journal-title":"Annu. Rev. Physiol."},{"key":"BFnm2237_CR19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1177\/108705710200700110","volume":"7","author":"DF Baxter","year":"2002","unstructured":"Baxter, D.F. et al. A novel membrane potential-sensitive fluorescent dye improves cell-based assays for ion channels. J. Biomol. Screen. 7, 79\u201385 (2002).","journal-title":"J. Biomol. Screen."},{"key":"BFnm2237_CR20","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.neuron.2008.09.001","volume":"59","author":"B Fakler","year":"2008","unstructured":"Fakler, B. & Adelman, J.P. Control of KCa channels by calcium nano\/microdomains. Neuron 59, 873\u2013881 (2008).","journal-title":"Neuron"},{"key":"BFnm2237_CR21","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1126\/science.1173869","volume":"325","author":"AS Shah","year":"2009","unstructured":"Shah, A.S., Ben Shahar, Y., Moninger, T.O., Kline, J.N. & Welsh, M.J. Motile cilia of human airway epithelia are chemosensory. Science 325, 1131\u20131134 (2009).","journal-title":"Science"},{"key":"BFnm2237_CR22","doi-asserted-by":"publisher","first-page":"8981","DOI":"10.1073\/pnas.1531172100","volume":"100","author":"TE Finger","year":"2003","unstructured":"Finger, T.E. et al. Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc. Natl. Acad. Sci. USA 100, 8981\u20138986 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm2237_CR23","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.1021\/jf070503p","volume":"55","author":"A Brockhoff","year":"2007","unstructured":"Brockhoff, A., Behrens, M., Massarotti, A., Appendino, G. & Meyerhof, W. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine and denatonium. J. Agric. Food Chem. 55, 6236\u20136243 (2007).","journal-title":"J. Agric. Food Chem."},{"key":"BFnm2237_CR24","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1002\/ar.20866","volume":"292","author":"A Sbarbati","year":"2009","unstructured":"Sbarbati, A. et al. Acyl homoserine lactones induce early response in the airway. Anat. Rec. (Hoboken) 292, 439\u2013448 (2009).","journal-title":"Anat. Rec. (Hoboken)"},{"key":"BFnm2237_CR25","doi-asserted-by":"publisher","first-page":"L453","DOI":"10.1152\/ajplung.00084.2007","volume":"293","author":"A Panebra","year":"2007","unstructured":"Panebra, A., Schwarb, M.R., Glinka, C.B. & Liggett, S.B. Heterogeneity of transcription factor expression and regulation in human airway epithelial and smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 293, L453\u2013L462 (2007).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"BFnm2237_CR26","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0026-895X(25)09637-3","volume":"36","author":"SB Liggett","year":"1989","unstructured":"Liggett, S.B. et al. Altered patterns of agonist-stimulated cAMP accumulation in cells expressing mutant \u03b22-adrenergic receptors lacking phosphorylation sites. Mol. Pharmacol. 36, 641\u2013646 (1989).","journal-title":"Mol. Pharmacol."},{"key":"BFnm2237_CR27","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1172\/JCI25840","volume":"116","author":"DW McGraw","year":"2006","unstructured":"McGraw, D.W. et al. Airway smooth muscle prostaglandin-EP1 receptors directly modulate \u03b22-adrenergic receptors within a unique heterodimeric complex. J. Clin. Invest. 116, 1400\u20131409 (2006).","journal-title":"J. Clin. Invest."},{"key":"BFnm2237_CR28","doi-asserted-by":"publisher","first-page":"L338","DOI":"10.1152\/ajplung.00328.2004","volume":"289","author":"XR Yang","year":"2005","unstructured":"Yang, X.R. et al. Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca2+ stores in pulmonary arterial smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 289, L338\u2013L348 (2005).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm2237_CR29","doi-asserted-by":"publisher","first-page":"L680","DOI":"10.1152\/ajplung.00067.2003","volume":"285","author":"WM Zhang","year":"2003","unstructured":"Zhang, W.M. et al. ET-1 activates Ca2+ sparks in PASMC: local Ca2+ signaling between inositol trisphosphate and ryanodine receptors. Am. J. Physiol. Lung Cell. Mol. Physiol. 285, L680\u2013L690 (2003).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm2237_CR30","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1126\/science.8235594","volume":"262","author":"H Cheng","year":"1993","unstructured":"Cheng, H., Lederer, W.J. & Cannell, M.B. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262, 740\u2013744 (1993).","journal-title":"Science"},{"key":"BFnm2237_CR31","doi-asserted-by":"publisher","first-page":"13020","DOI":"10.1073\/pnas.0405074101","volume":"101","author":"KM Small","year":"2004","unstructured":"Small, K.M. et al. Polymorphisms of the cardiac presynaptic \u03b12C adrenergic receptors: diverse intragenic variability with haplotype-specific functional effects. Proc. Natl. Acad. Sci. USA 101, 13020\u201313025 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm2237_CR32","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K.J. & Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2013\u0394\u0394C t) method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"BFnm2237_CR33","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1172\/JCI30489","volume":"117","author":"DW McGraw","year":"2007","unstructured":"McGraw, D.W. et al. Crosstalk between Gi and Gq\/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation. J. Clin. Invest. 117, 1391\u20131398 (2007).","journal-title":"J. Clin. Invest."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.2237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.2237","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.2237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T23:58:46Z","timestamp":1740614326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.2237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,24]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["BFnm2237"],"URL":"https:\/\/doi.org\/10.1038\/nm.2237","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.6185956.10214058","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.6262064","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.6457058","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.6770054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.6325056","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.6235054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6185956.10729055","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,24]]},"assertion":[{"value":"4 February 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}