{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:07:06Z","timestamp":1779325626860,"version":"3.51.4"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ejphar.2025.178257","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T07:09:07Z","timestamp":1760512147000},"page":"178257","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Enhancement of chloride transport via Ca2+ mobilization in airway epithelial cells by DS-1039, a novel selective GPR39 agonist"],"prefix":"10.1016","volume":"1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6326-0983","authenticated-orcid":false,"given":"Satoshi","family":"Muneoka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Inomata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6210-8699","authenticated-orcid":false,"given":"Kei","family":"Enomoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Nakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munetada","family":"Haruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Hama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Kanki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Terashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiori","family":"Egashira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Kamei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Tomimori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.178257_bib1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ppul.20771","article-title":"Effect of zinc supplementation on respiratory tract infections in children with cystic fibrosis","volume":"43","author":"Abdulhamid","year":"2008","journal-title":"Pediatr. Pulmonol."},{"issue":"50","key":"10.1016\/j.ejphar.2025.178257_bib2","doi-asserted-by":"crossref","first-page":"51804","DOI":"10.1074\/jbc.M406581200","article-title":"Extracellular zinc triggers ERK-dependent activation of Na+\/H+ exchange in colonocytes mediated by the zinc-sensing receptor","volume":"279","author":"Azriel-Tamir","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178257_bib3","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1111\/cns.14174","article-title":"Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39","volume":"29","author":"Cao","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.ejphar.2025.178257_bib4","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1126\/science.1163518","article-title":"TMEM16A, a Membrane protein associated with calcium-dependent chloride channel activity","volume":"322","author":"Caputo","year":"2008","journal-title":"Science"},{"issue":"7","key":"10.1016\/j.ejphar.2025.178257_bib5","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1073\/pnas.1415739112","article-title":"A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland","volume":"112","author":"Catal\u00e1n","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejphar.2025.178257_bib6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jtemb.2013.10.003","article-title":"Plasma zinc in adults with cystic fibrosis: correlations with clinical outcomes","volume":"28","author":"Damphousse","year":"2014","journal-title":"J. Trace Elem. Med. Biol."},{"key":"10.1016\/j.ejphar.2025.178257_bib7","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1164\/rccm.201908-1641OC","article-title":"TMEM16A potentiation: a novel therapeutic approach for the treatment of cystic fibrosis","volume":"201","author":"Danahay","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ejphar.2025.178257_bib8","doi-asserted-by":"crossref","first-page":"7074","DOI":"10.1074\/jbc.M704323200","article-title":"The constitutively active orphan G-protein-coupled receptor GPR39 protects from cell death by increasing secretion of pigment epithelium-derived growth factor","volume":"283","author":"Dittmer","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.178257_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.175677","article-title":"The TMEM16A blockers benzbromarone and MONNA cause intracellular Ca2+-release in mouse bronchial smooth muscle cells","volume":"947","author":"Dwivedi","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178257_bib10","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1210\/me.2007-0055","article-title":"GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue","volume":"21","author":"Egerod","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ejphar.2025.178257_bib11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3390\/nu11010150","article-title":"Zinc nutritional status in patients with cystic fibrosis","volume":"11","author":"Escobedo Monge","year":"2019","journal-title":"Nutrients"},{"key":"10.1016\/j.ejphar.2025.178257_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101207","article-title":"Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist","volume":"49","author":"Grunddal","year":"2021","journal-title":"Mol. Metab."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178257_bib14","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3390\/ijms19020439","article-title":"The zinc sensing receptor, ZnR\/GPR39, in health and disease","volume":"19","author":"Hershfinkel","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.178257_bib16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1210\/en.2006-0933","article-title":"GPR39 signaling is stimulated by zinc ions but not by obestatin","volume":"148","author":"Holst","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2025.178257_bib43","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1210\/en.2008-1251","article-title":"Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo during aging and diet-induced obesity","volume":"150","author":"Holst","year":"2009","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2025.178257_bib17","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ebiom.2017.12.025","article-title":"Zinc deficiency via a splice switch in zinc importer ZIP2\/SLC39A2 causes cystic fibrosis-associated MUC5AC hypersecretion in airway epithelial cells","volume":"27","author":"Kamei","year":"2018","journal-title":"EBioMedicine"},{"issue":"3","key":"10.1016\/j.ejphar.2025.178257_bib18","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1538\/expanim.62.173","article-title":"Anesthetic effects of a mixture of medetomidine, midazolam and butorphanol in two strains of mice","volume":"62","author":"Kirihara","year":"2013","journal-title":"Exp. Anim."},{"issue":"8","key":"10.1016\/j.ejphar.2025.178257_bib19","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.3390\/ijms22083872","article-title":"The zinc-sensing receptor GPR39 in physiology and as a pharmacological target","volume":"22","author":"Laitakari","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.178257_bib21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jad.2016.05.007","article-title":"Potential antidepressant-like properties of the TC G-1008, a GPR39 (zinc receptor) agonist","volume":"201","author":"M\u0142yniec","year":"2016","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.ejphar.2025.178257_bib22","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jpeds.2012.11.034","article-title":"Pitfalls of drug development: lessons learned from trials of denufosol in cystic fibrosis","volume":"162","author":"Moss","year":"2013","journal-title":"J. Pediatr."},{"key":"10.1016\/j.ejphar.2025.178257_bib23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ejphar.2018.07.045","article-title":"G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions","volume":"834","author":"Muneoka","year":"2018","journal-title":"Eur. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178257_bib24","doi-asserted-by":"crossref","first-page":"G707","DOI":"10.1152\/ajpgi.00101.2010","article-title":"Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon","volume":"299","author":"Nanda Kumar","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178257_bib25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3390\/nu10020199","article-title":"Zinc and skin disorders","volume":"10","author":"Ogawa","year":"2018","journal-title":"Nutrients"},{"issue":"5","key":"10.1016\/j.ejphar.2025.178257_bib26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ygeno.2011.06.008","article-title":"Differential global gene expression in cystic fibrosis nasal and bronchial epithelium","volume":"98","author":"Ogilvie","year":"2011","journal-title":"Genomics"},{"key":"10.1016\/j.ejphar.2025.178257_bib28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cellsig.2017.01.024","article-title":"GPCR desensitization: acute and prolonged phases","volume":"41","author":"Rajagopal","year":"2018","journal-title":"Cell. Signal."},{"key":"10.1016\/j.ejphar.2025.178257_bib29","doi-asserted-by":"crossref","first-page":"14875","DOI":"10.1074\/jbc.C109.000869","article-title":"Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl\u2013secretory channel in mouse airways","volume":"284","author":"Rock","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.178257_bib30","article-title":"Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner","volume":"25","author":"Saha","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"10.1016\/j.ejphar.2025.178257_bib44","doi-asserted-by":"crossref","first-page":"L936","DOI":"10.1152\/ajplung.00354.2003","article-title":"CFTR involvement in nasal potential differences in mice and pigs studied using a thiazolidinone CFTR inhibitor","volume":"287","author":"Salinas","year":"2004","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.ejphar.2025.178257_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110160","article-title":"A G-protein coupled receptor 39 agonist stimulates proliferation of keratinocytes via an ERK-dependent pathway","volume":"127","author":"Satianrapapong","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejphar.2025.178257_bib32","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1124\/mol.116.106112","article-title":"Discovery and characterization of novel GPR39 agonists allosterically modulated by zinc","volume":"90","author":"Sato","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178257_bib33","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2008.09.003","article-title":"Expression cloning of TMEM16A as a calcium-activated chloride channel subunit","volume":"134","author":"Schroeder","year":"2008","journal-title":"Cell"},{"issue":"Suppl. 2","key":"10.1016\/j.ejphar.2025.178257_bib34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jcf.2004.05.032","article-title":"Basic protocol for transepithelial nasal potential difference measurements","volume":"3","author":"Sch\u00fcler","year":"2004","journal-title":"J. Cyst. Fibros."},{"issue":"34","key":"10.1016\/j.ejphar.2025.178257_bib35","doi-asserted-by":"crossref","first-page":"26097","DOI":"10.1074\/jbc.M110.107490","article-title":"Zinc released from injured cells is acting via the Zn2+-sensing receptor, ZnR, to trigger signaling leading to epithelial repair","volume":"285","author":"Sharir","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178257_bib36","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.bbadis.2017.01.009","article-title":"The Zn2+-sensing receptor, ZnR\/GPR39, upregulates colonocytic Cl- absorption, via basolateral KCC1, and reduces fluid loss","volume":"1863","author":"Sunuwar","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178257_bib37","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1164\/rccm.201206-1150OC","article-title":"A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection","volume":"187","author":"Tiringer","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ejphar.2025.178257_bib38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.plefa.2007.12.005","article-title":"Oral DHA supplementation in \u0394F508 homozygous cystic fibrosis patients","volume":"78","author":"Van Biervliet","year":"2008","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178257_bib39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1006\/abio.1996.0377","article-title":"A microplate assay measuring chloride ion channel activity","volume":"241","author":"West","year":"1996","journal-title":"Anal. Biochem."},{"issue":"15","key":"10.1016\/j.ejphar.2025.178257_bib40","doi-asserted-by":"crossref","first-page":"8200","DOI":"10.3390\/ijms22158200","article-title":"Role of GPR39 in neurovascular homeostasis and disease","volume":"22","author":"Xu","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.178257_bib41","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nature07313","article-title":"TMEM16A confers receptor-activated calcium-dependent chloride conductance","volume":"455","author":"Yang","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2025.178257_bib42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0047686","article-title":"GPR39 is coupled to TMEM16A in intestinal fibroblast-like cells","volume":"7","author":"Zeng","year":"2012","journal-title":"PLoS One"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925010118?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925010118?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:33:06Z","timestamp":1779323586000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925010118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":40,"alternative-id":["S0014299925010118"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178257","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enhancement of chloride transport via Ca2+ mobilization in airway epithelial cells by DS-1039, a novel selective GPR39 agonist","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178257","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"178257"}}