{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:51:34Z","timestamp":1773449494061,"version":"3.50.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["43028659"],"award-info":[{"award-number":["43028659"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2018,1]]},"DOI":"10.1016\/j.lfs.2017.11.034","type":"journal-article","created":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T02:04:03Z","timestamp":1511402643000},"page":"99-109","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Crosstalk between mAChRM3 and \u03b22AR, via acetylcholine PI3\/PKC\/PBEP1\/Raf-1 MEK1\/2\/ERK1\/2 pathway activation, in human bronchial epithelial cells after long-term cigarette smoke exposure"],"prefix":"10.1016","volume":"192","author":[{"given":"Giusy Daniela","family":"Albano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bonanno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Moscato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Anzalone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Di Sano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Riccobono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally E.","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirella","family":"Profita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.lfs.2017.11.034_bb0005","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1513\/pats.200504-038SR","article-title":"Beta2-agonist and anticholinergic drugs in the treatment of lung disease","volume":"2","author":"Proskocil","year":"2005","journal-title":"Proc. Am. Thorac. Soc."},{"issue":"11","key":"10.1016\/j.lfs.2017.11.034_bb0010","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/cvr\/27.11.1948","article-title":"Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction","volume":"27","author":"Bartel","year":"1993","journal-title":"Cardiovasc. Res."},{"issue":"3","key":"10.1016\/j.lfs.2017.11.034_bb0015","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cardiores.2004.04.022","article-title":"Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart","volume":"63","author":"Pepe","year":"2004","journal-title":"Cardiovasc. Res."},{"issue":"3","key":"10.1016\/j.lfs.2017.11.034_bb0020","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1513\/pats.200402-010MS","article-title":"Interactions between corticosteroids and beta2-agonists in asthma and chronic obstructive pulmonary disease","volume":"1","author":"Johnson","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"issue":"4","key":"10.1016\/j.lfs.2017.11.034_bb0025","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1513\/pats.200504-043SR","article-title":"Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease","volume":"2","author":"Belmonte","year":"2005","journal-title":"Proc. Am. Thorac. Soc."},{"issue":"2","key":"10.1016\/j.lfs.2017.11.034_bb0030","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1124\/mol.107.044750","article-title":"M3 muscarinic acetylcholine receptor-mediated signaling is regulated by distinct mechanisms","volume":"74","author":"Luo","year":"2008","journal-title":"Mol. Pharmacol."},{"issue":"7","key":"10.1016\/j.lfs.2017.11.034_bb0035","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1074\/jbc.M008827200","article-title":"Phosphorylation of the Gq\/11-coupled m3-muscarinic receptor is involved in receptor activation of the ERK-1\/2 mitogen-activated protein kinase pathway","volume":"276","author":"Budd","year":"2001","journal-title":"J. Biol. Chem."},{"issue":"22\u221223","key":"10.1016\/j.lfs.2017.11.034_bb0040","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/S0024-3205(01)01048-7","article-title":"Novel signalling events mediated by muscarinic receptor subtypes","volume":"68","author":"B\u00fcnemann","year":"2001","journal-title":"Life Sci."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0045","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/abbi.2000.1761","article-title":"Activation of m3 muscarinic receptors induces rapid tyrosine phosphorylation of p125(FAK), p130(cas), and paxillin in rat pancreatic acini","volume":"377","author":"Rosado","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"issue":"34","key":"10.1016\/j.lfs.2017.11.034_bb0050","doi-asserted-by":"crossref","first-page":"19949","DOI":"10.1074\/jbc.270.34.19949","article-title":"Rapid and persistent desensitization of m3 muscarinic acetylcholine receptor-stimulated phospholipase D. Concomitant sensitization of phospholipase C","volume":"270","author":"Schmidt","year":"1995","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.lfs.2017.11.034_bb0055","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1476-5381.1990.tb14697.x","article-title":"Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle","volume":"99","author":"Roffel","year":"1990","journal-title":"Br. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.lfs.2017.11.034_bb0060","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0014-2999(88)90331-7","article-title":"Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists","volume":"156","author":"Meurs","year":"1988","journal-title":"Eur. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.lfs.2017.11.034_bb0065","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1124\/mol.60.2.321","article-title":"G protein-coupled receptor kinases 3 and 6 use different pathways to desensitize the endogenous M3 muscarinic acetylcholine receptor in human SH-SY5Y cells","volume":"60","author":"Willets","year":"2001","journal-title":"Mol. Pharmacol."},{"issue":"11\u221212","key":"10.1016\/j.lfs.2017.11.034_bb0070","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/0024-3205(95)00033-3","article-title":"Multiple mechanisms involving protein phosphorylation are linked to desensitization of muscarinic receptors","volume":"56","author":"Hosey","year":"1995","journal-title":"Life Sci."},{"issue":"12","key":"10.1016\/j.lfs.2017.11.034_bb0075","doi-asserted-by":"crossref","first-page":"9026","DOI":"10.1074\/jbc.275.12.9026","article-title":"Identification of Gbetagamma binding sites in the third intracellular loop of the M(3)-muscarinic receptor and their role in receptor regulation","volume":"275","author":"Wu","year":"2000","journal-title":"J. Biol. Chem."},{"issue":"18","key":"10.1016\/j.lfs.2017.11.034_bb0080","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1093\/emboj\/20.18.5129","article-title":"Beta-arrestin- and c-Src-dependent degradation of G-protein-coupled receptor kinase 2","volume":"20","author":"Penela","year":"2001","journal-title":"EMBO J."},{"issue":"6966","key":"10.1016\/j.lfs.2017.11.034_bb0085","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nature02158","article-title":"Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2","volume":"426","author":"Lorenz","year":"2003","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.lfs.2017.11.034_bb0090","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1615\/CritRevOncog.2014012000","article-title":"Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer","volume":"19","author":"Yesilkanal","year":"2014","journal-title":"Crit Rev Oncog. Crit Rev Oncog."},{"issue":"6749","key":"10.1016\/j.lfs.2017.11.034_bb0095","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/43686","article-title":"Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP","volume":"401","author":"Yeung","year":"1999","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.lfs.2017.11.034_bb0100","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1128\/MCB.20.9.3079-3085.2000","article-title":"Mechanism of suppression of the Raf\/MEK\/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein","volume":"20","author":"Yeung","year":"2000","journal-title":"Mol. Cell. Biol."},{"issue":"5","key":"10.1016\/j.lfs.2017.11.034_bb0105","article-title":"Long-term exposure to cigarette smoke extract induces hypomethylation at the RUNX3 and IGF2-H19 loci in immortalized human urothelial cells","volume":"8","author":"Jennifer","year":"2013","journal-title":"PLoS One"},{"issue":"5","key":"10.1016\/j.lfs.2017.11.034_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2015.02.006","article-title":"IL-13 desensitizes \u03b22-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase\/G protein receptor kinase 2 mechanism","volume":"135","author":"Albano","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"issue":"4","key":"10.1016\/j.lfs.2017.11.034_bb0115","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.phrs.2012.05.007","article-title":"Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects","volume":"66","author":"Santus","year":"2012","journal-title":"Pharmacol. Res."},{"issue":"1\u20133","key":"10.1016\/j.lfs.2017.11.034_bb0120","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejphar.2012.07.002","article-title":"\u03b2\u2082-adrenoceptors and muscarinic receptors mediate opposing effects on endothelin-1 expression in human lung fibroblasts","volume":"691","author":"Ahmedat","year":"2012","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0125","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1124\/jpet.110.167007","article-title":"Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models","volume":"334","author":"Bouyssou","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.lfs.2017.11.034_bb0130","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.coph.2014.03.005","article-title":"Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway","volume":"16","author":"Pera","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"issue":"4","key":"10.1016\/j.lfs.2017.11.034_bb0135","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0026-895X(24)12545-X","article-title":"Cross talk between m3-muscarinic and beta(2)-adrenergic receptors at the level of receptor phosphorylation and desensitization","volume":"56","author":"Budd","year":"1999","journal-title":"Mol. Pharmacol."},{"issue":"1\u20132","key":"10.1016\/j.lfs.2017.11.034_bb0140","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.lfs.2011.04.025","article-title":"Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro","volume":"89","author":"Profita","year":"2011","journal-title":"Life Sci."},{"issue":"3","key":"10.1016\/j.lfs.2017.11.034_bb0145","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1046\/j.1440-1681.1999.03016.x","article-title":"The cholinergic \u2018pitfall\u2019: acetylcholine, a universal cell molecule in biological systems, including humans","volume":"26","author":"Wessler","year":"1999","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"issue":"5","key":"10.1016\/j.lfs.2017.11.034_bb0150","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1210\/en.2003-1728","article-title":"Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells","volume":"145","author":"Proskocil","year":"2004","journal-title":"Endocrinology"},{"issue":"7","key":"10.1016\/j.lfs.2017.11.034_bb0155","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1096\/fj.07-102459","article-title":"Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle","volume":"22","author":"Deshpande","year":"2008","journal-title":"FASEB J."},{"issue":"2","key":"10.1016\/j.lfs.2017.11.034_bb0160","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1096\/fj.13-240226","article-title":"Exploiting functional domains of GRK2\/3 to alter the competitive balance of pro- and anticontractile signaling in airway smoothmuscle","volume":"28","author":"Deshpande","year":"2014","journal-title":"FASEB J."},{"issue":"6","key":"10.1016\/j.lfs.2017.11.034_bb0165","first-page":"394","article-title":"Understanding perspectives of signalling mechanisms regulating PEBP1 function","volume":"34","author":"Rajkumar","year":"2016","journal-title":"Cell BiochemFunct."},{"issue":"1\u20133","key":"10.1016\/j.lfs.2017.11.034_bb0170","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejphar.2007.12.029","article-title":"Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB\/ERK-dependent mechanism","volume":"582","author":"Profita","year":"2008","journal-title":"Eur. J. Pharmacol."},{"issue":"12","key":"10.1016\/j.lfs.2017.11.034_bb0175","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.bbadis.2013.06.009","article-title":"Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative\/nitrosative stress in human bronchial epithelial cell line","volume":"1832","author":"Profita","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"issue":"15","key":"10.1016\/j.lfs.2017.11.034_bb0180","doi-asserted-by":"crossref","first-page":"13061","DOI":"10.1074\/jbc.M210015200","article-title":"Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein","volume":"278","author":"Corbit","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.lfs.2017.11.034_bb0185","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/9063842","article-title":"Autocrine acetylcholine, induced by IL-17A via NF\u03baB and ERK1\/2 pathway activation, promotes MUC5AC and IL-8 synthesis in bronchial epithelial cells","volume":"2016","author":"Montalbano","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.lfs.2017.11.034_bb0190","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.2147\/TCRM.S84151","article-title":"Pharmacologic rationale underlying the therapeutic effects of tiotropium\/olodaterol in COPD","volume":"11","author":"Pelaia","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0195","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/01.mcp.0000198066.73328.3a","article-title":"Anticholinergic agents in asthma: chronic bronchodilator therapy, relief of acute severe asthma, reduction of chronic viral inflammation and prevention of airway remodeling","volume":"12","author":"Kanazawa","year":"2006","journal-title":"Curr. Opin. Pulm. Med."},{"issue":"4","key":"10.1016\/j.lfs.2017.11.034_bb0200","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0873-2159(15)30264-6","article-title":"Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD","volume":"14","author":"Powrie","year":"2008","journal-title":"Rev. Port. Pneumol."},{"issue":"9","key":"10.1016\/j.lfs.2017.11.034_bb0205","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.rmed.2011.03.020","article-title":"TGF\u03b2-induced matrix production by bronchial fibroblasts in asthma: budesonide and formoterol effects","volume":"105","author":"Todorova","year":"2011","journal-title":"Respir. Med."},{"key":"10.1016\/j.lfs.2017.11.034_bb0210","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1465-9921-7-73","article-title":"Muscarinic receptor signaling in the pathophysiology of asthma and COPD","volume":"7","author":"Gosens","year":"2006","journal-title":"Respir. Res."},{"issue":"18","key":"10.1016\/j.lfs.2017.11.034_bb0215","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1056\/NEJMoa1008770","article-title":"NationalHeart, lung, and blood institute asthma clinical research network. Tiotropium bromide step-up therapy for adults with uncontrolled asthma","volume":"363","author":"Peters","year":"2010","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0220","first-page":"L69","article-title":"The small heat shock-related protein, HSP20, is a cAMP-dependent protein kinase substrate that is involved in airway smooth muscle relaxation","volume":"294","author":"Komalavilas","year":"2008","journal-title":"Am. J. Phys. Lung Cell. Mol. Phys."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0225","first-page":"27","article-title":"HSP20 phosphorylation and airway smooth muscle relaxation","volume":"2009","author":"Ba","year":"2009","journal-title":"Cell Health Cytoskelet."},{"issue":"1","key":"10.1016\/j.lfs.2017.11.034_bb0230","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1172\/JCI116969","article-title":"Beta-adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP-dependent and -independent mechanisms","volume":"93","author":"Kume","year":"1994","journal-title":"J. Clin. Invest."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320517306112?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320517306112?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:13:49Z","timestamp":1758399229000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320517306112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":46,"alternative-id":["S0024320517306112"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2017.11.034","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Crosstalk between mAChRM3 and \u03b22AR, via acetylcholine PI3\/PKC\/PBEP1\/Raf-1 MEK1\/2\/ERK1\/2 pathway activation, in human bronchial epithelial cells after long-term cigarette smoke exposure","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2017.11.034","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}