{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:26:42Z","timestamp":1771633602974,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"publisher","award":["18KI0174"],"award-info":[{"award-number":["18KI0174"]}],"id":[{"id":"10.13039\/501100003837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015644","name":"Pancreas Research Foundation of Japan","doi-asserted-by":"publisher","award":["H26-7"],"award-info":[{"award-number":["H26-7"]}],"id":[{"id":"10.13039\/100015644","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Osaka Community Foundation","award":["2019IGAKU10"],"award-info":[{"award-number":["2019IGAKU10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of HCO3\u2212 in pancreatic juice from the rat pancreas were measured. The A2A adenosine receptor colocalized with ezrin, an A-kinase anchoring protein, in the luminal membrane of duct cells in the mouse and guinea pig pancreas. However, a strong signal ascribed to A2B adenosine receptors was detected in insulin-positive \u03b2 cells in islets of Langerhans. The A2A adenosine receptor agonist 4-[2-[[6-Amino-9-(N-ethyl-\u03b2-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS 21680) stimulated HCO3\u2212-rich fluid secretion from the rat pancreas. These results indicate that A2A adenosine receptors may be, at least in part, involved in the exocrine secretion of pancreatic duct cells via acini-to-duct signaling. The adenosine receptors may be a potential therapeutic target for cancer as well as exocrine dysfunctions of the pancreas.<\/jats:p>","DOI":"10.3390\/ijms20215329","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T11:05:18Z","timestamp":1572001518000},"page":"5329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Expression of Adenosine Receptors in Rodent Pancreas"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-5683","authenticated-orcid":false,"given":"Mikio","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Cell Physiology, Institute of Biomedical Science, Kansai Medical University, 2-5-1 shin-machi, Hirakata, Osaka 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C151","DOI":"10.1152\/ajpcell.00089.2012","article-title":"An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells","volume":"303","author":"Hayashi","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C673","DOI":"10.1152\/ajpcell.00196.2012","article-title":"Purinergic regulation of CFTR and Ca2+-activated Cl\u2212 channels and K+ channels in human pancreatic duct epithelium","volume":"304","author":"Wang","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a009746","DOI":"10.1101\/cshperspect.a009746","article-title":"The cystic fibrosis of exocrine pancreas","volume":"3","author":"Wilschanski","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00424-018-2116-1","article-title":"Electrophysiological properties of anion exchangers in the luminal membrane of guinea pig pancreatic duct cells","volume":"470","author":"Andharia","year":"2018","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sakata, N., Yoshimatsu, G., and Kodama, S. (2019). Development and Characteristics of Pancreatic Epsilon Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081867"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1530\/JOE-11-0434","article-title":"Purinergic signalling in the pancreas in health and disease","volume":"213","author":"Burnstock","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29441","DOI":"10.1074\/jbc.M602480200","article-title":"ATP-consuming and ATP-generating enzymes secreted by pancreas","volume":"281","author":"Yegutkin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00424-007-0403-3","article-title":"Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport","volume":"456","author":"Novak","year":"2008","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s00424-016-1806-9","article-title":"The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells","volume":"468","author":"Hayashi","year":"2016","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1472-8206.2000.tb00017.x","article-title":"Subtypes of adenosine receptors on pancreatic exocrine secretion in anaesthetized dogs","volume":"14","author":"Iwatsuki","year":"2000","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0014-2999(87)90786-2","article-title":"Evidence for an inhibitory A1 subtype adenosine receptor on pancreatic insulin-secreting cells","volume":"136","author":"Bertrand","year":"1987","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","first-page":"E473","article-title":"Membrane and intracellular effects of adenosine in mouse pancreatic \u03b2-cells","volume":"257","author":"Bertrand","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrendo.2015.10","article-title":"Adenosine signalling in diabetes mellitus\u2014pathophysiology and therapeutic considerations","volume":"11","author":"Antonioli","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ygcen.2013.02.011","article-title":"Possible involvement of A2A and A3 receptors in modulation of insulin secretion and \u03b2-cell survival in mouse pancreatic islets","volume":"187","author":"Ohtani","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1096\/fj.07-8213com","article-title":"Adenosine receptor activation ameliorates type 1 diabetes","volume":"21","author":"Bleich","year":"2007","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E952","DOI":"10.1152\/ajpendo.00641.2007","article-title":"Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic \u03b1-cells by extracellular ATP and purinergic receptors","volume":"294","author":"Filiputti","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.2337\/db13-0614","article-title":"Diminished adenosine A1 receptor expression in pancreatic \u03b1-cells may contribute to the pathology of type 1 diabetes","volume":"62","author":"Yip","year":"2013","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0006-2952(00)00570-0","article-title":"Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells","volume":"61","author":"Fredholm","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1679\/aohc.64.59","article-title":"Morphological changes in pancreatic islets of KATP channel-deficient mice: The involvement of KATP channels in the survival of insulin cells and the maintenance of islet architecture","volume":"64","author":"Winarto","year":"2001","journal-title":"Arch. Histol. Cytol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1113\/jphysiol.1975.sp011149","article-title":"Secretion of electrolytes by the pancreas of the anaesthetized rat","volume":"252","author":"Sewell","year":"1975","journal-title":"J. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1113\/jphysiol.1972.sp009963","article-title":"The action of secretin, cholecystokinin-pancreozymin and caerulein on pancreatic secretion in the rat","volume":"225","author":"Dockray","year":"1972","journal-title":"J. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/MPA.0b013e318264c302","article-title":"Ion transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by secretin, VIP, acetylcholine, and purinergic receptors","volume":"42","author":"Wang","year":"2012","journal-title":"Pancreas"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"C819","DOI":"10.1152\/ajpcell.1998.274.3.C819","article-title":"Type II protein kinase A regulates CFTR in airway, pancreatic, and intestinal cells","volume":"274","author":"Steagall","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"C417","DOI":"10.1152\/ajpcell.2000.278.2.C417","article-title":"PKA holoenzyme is functionally coupled to CFTR by AKAPs","volume":"278","author":"Huang","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1113\/jphysiol.2003.056697","article-title":"Purinergic regulation of epithelial transport","volume":"555","author":"Bucheimer","year":"2004","journal-title":"J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1124\/mol.109.059345","article-title":"Adenylyl cyclase\u2013A-kinase anchoring protein complexes: The next dimension in cAMP signaling","volume":"76","author":"Dessauer","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1039\/b924455g","article-title":"CFTR chloride channel in the apical compartments: Spatiotemporal coupling to its interacting partners","volume":"2","author":"Li","year":"2010","journal-title":"Integr. Biol. (Camb.)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1124\/mol.117.110825","article-title":"cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic Signaling Complexes","volume":"93","author":"Johnstone","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1113\/jphysiol.2012.249698","article-title":"Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation","volume":"591","author":"Sabbatini","year":"2013","journal-title":"J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12949","DOI":"10.1074\/jbc.RA118.003378","article-title":"AC6 is the major adenylate cyclase forming a diarrheagenic protein complex with cystic fibrosis transmembrane conductance regulator in cholera","volume":"293","author":"Thomas","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/febs.13969","article-title":"Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity","volume":"284","author":"Guinzberg","year":"2017","journal-title":"FEBS J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1365-201x.1998.00330.x","article-title":"A2 adenosine receptors in Mongolian gerbil middle ear epithelium and their regulation of Cl\u2212 secretion","volume":"163","author":"Furukawa","year":"1998","journal-title":"Acta Physiol. Scand."},{"key":"ref_33","first-page":"F104","article-title":"Regulation of cAMP-dependent chloride channels in DC1 immortalized rabbit distal tubule cells in culture","volume":"276","author":"Rubera","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1016\/j.yexcr.2009.06.005","article-title":"Cholesterol-dependent regulation of adenosine A2A receptor-mediated anion secretion in colon epithelial cells","volume":"315","author":"Lam","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_35","first-page":"1639","article-title":"The impact of adenosine and A2B receptors on glucose homoeostasis","volume":"58","author":"Verspohl","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"39271","DOI":"10.1074\/jbc.M109.098293","article-title":"Adenosine A2A receptor is involved in cell surface expression of A2B receptor","volume":"285","author":"Moriyama","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13593","DOI":"10.18632\/oncotarget.24423","article-title":"Adenosine A2A receptor ligand recognition and signaling is blocked by A2B receptors","volume":"9","author":"Hinz","year":"2018","journal-title":"Oncotarget"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s11302-012-9350-3","article-title":"A2B adenosine receptor blockade inhibits growth of prostate cancer cells","volume":"9","author":"Wei","year":"2013","journal-title":"Purinergic Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"48755","DOI":"10.18632\/oncotarget.17835","article-title":"The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway","volume":"8","author":"Zhou","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.humpath.2010.04.008","article-title":"Hypoxia-inducible adenosine A2B receptor modulates proliferation of colon carcinoma cells","volume":"41","author":"Ma","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1158\/0008-5472.CAN-16-0544","article-title":"Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis","volume":"76","author":"Mittal","year":"2016","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E9640","DOI":"10.1073\/pnas.1809695115","article-title":"Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment","volume":"115","author":"Lan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34554","DOI":"10.18632\/oncotarget.26177","article-title":"Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signaling","volume":"9","author":"Horigome","year":"2018","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1523\/JNEUROSCI.1118-18.2019","article-title":"CD73 Promotes Glioblastoma Pathogenesis and Enhances Its Chemoresistance via A2B Adenosine Receptor Signaling","volume":"39","author":"Yan","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1152\/ajplegacy.1958.194.3.535","article-title":"Pancreatic secretion in the rat","volume":"194","author":"Grossman","year":"1958","journal-title":"Am. J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:29:29Z","timestamp":1760189369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,25]]},"references-count":47,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["ijms20215329"],"URL":"https:\/\/doi.org\/10.3390\/ijms20215329","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,25]]}}}