{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:43:40Z","timestamp":1790318620557,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["HL103405"],"award-info":[{"award-number":["HL103405"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Background and Purpose<\/jats:title>While selective, bitter tasting, TAS2R agonists can relax agonist\u2010contracted airway smooth muscle (ASM<\/jats:styled-content>), their mechanism of action is unclear. However, ASM<\/jats:styled-content> contraction is regulated by Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> signalling and Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> sensitivity. We have therefore investigated how the TAS2R10<\/jats:styled-content> agonists chloroquine, quinine and denotonium regulate contractile agonist\u2010induced Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> signalling and sensitivity.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Airways in mouse lung slices were contracted with either methacholine (MCh<\/jats:styled-content>) or 5HT and bronchodilation assessed using phase\u2010contrast microscopy. Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> signalling was measured with 2\u2010photon fluorescence microscopy of ASM<\/jats:styled-content> cells loaded with Oregon Green, a Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content>\u2010sensitive indicator (with or without caged\u2010IP<\/jats:styled-content>3<\/jats:sub>). Effects on Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM<\/jats:styled-content> cells to Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content>.<\/jats:p><\/jats:sec>Key Results<\/jats:title>The TAS2R10<\/jats:styled-content> agonists dilated airways constricted by either MCh<\/jats:styled-content> or 5HT, accompanied by inhibition of agonist\u2010induced Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> oscillations. However, in non\u2010contracted airways, TAS2R10<\/jats:styled-content> agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> signals in ASM<\/jats:styled-content> cells. Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> increases mediated by the photolysis of caged\u2010IP<\/jats:styled-content>3<\/jats:sub> were also attenuated by chloroquine, quinine and denotonium. In Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content>\u2010permeabilized ASM<\/jats:styled-content> cells, the TAS2R10<\/jats:styled-content> agonists dilated MCh<\/jats:styled-content>\u2010 and 5HT\u2010constricted airways.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>TAS2R10<\/jats:styled-content> agonists reversed bronchoconstriction by inhibiting agonist\u2010induced Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> oscillations while simultaneously reducing the Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> sensitivity of ASM<\/jats:styled-content> cells. Reduction of Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> oscillations may be due to inhibition of Ca2+<\/jats:sup><\/jats:roman><\/jats:styled-content> release through IP<\/jats:styled-content>3<\/jats:sub> receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12460","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T02:07:06Z","timestamp":1381543626000},"page":"646-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity"],"prefix":"10.1111","volume":"171","author":[{"given":"Xiahui","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(88)90081-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12444"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00317.2003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-34"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00494.2005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90288.2008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90559.2008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80706-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.423806"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0096OC"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2951"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0214OC"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0403OC"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2237"},{"issue":"4","key":"e_1_2_8_16_1","first-page":"L659","article-title":"Role of ryanodine receptor channels in Ca2+ oscillations of porcine tracheal smooth muscle","volume":"272","author":"Kannan MS","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2011.02308.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"8701","DOI":"10.1016\/S0021-9258(17)37024-2","article-title":"Phosphorylation of the inositol 1,4,5\u2010trisphosphate receptor by cyclic GMP\u2010dependent protein kinase","volume":"269","author":"Komalavilas P","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_8_19_1","first-page":"407","article-title":"Intercellular calcium signaling and flash photolysis of caged compounds. 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