{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:18Z","timestamp":1791928878168,"version":"4.3.4"},"reference-count":58,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"1","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2025,1,21]]},"DOI":"10.1167\/iovs.66.1.46","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T11:31:06Z","timestamp":1737459066000},"page":"46","source":"Crossref","is-referenced-by-count":2,"title":["Pyrimidinergic P2Y1-Like Nucleotide Receptors Are Functional in Rat Conjunctival Goblet Cells"],"prefix":"10.1167","volume":"66","author":[{"given":"Ketil A.","family":"Fj\u00e6rvoll","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"},{"name":"Division of Head, Neck and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Medical Student Research Program, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haakon K.","family":"Fj\u00e6rvoll","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"},{"name":"Division of Head, Neck and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Medical Student Research Program, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglu","family":"Yang","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Bair","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor P.","family":"Utheim","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"},{"name":"Division of Head, Neck and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Medical Student Research Program, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlene A.","family":"Dartt","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.exer.2018.11.018","article-title":"Resolvin D1, but not resolvin E1, transactivates the epidermal growth factor receptor to increase intracellular calcium and glycoconjugate secretion in rat and human conjunctival goblet cells","volume":"180","author":"Kaye","year":"2019","journal-title":"Exp Eye Res"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exer.2013.10.008","article-title":"Complexity of the tear film: importance in homeostasis and dysfunction during disease","volume":"117","author":"Dartt","year":"2013","journal-title":"Exp Eye Res"},{"issue":"4","key":"bib3","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1097\/ICO.0b013e3181f7f363","article-title":"The economic burden of dry eye disease in the United States: a decision tree analysis","volume":"30","author":"Yu","year":"2011","journal-title":"Cornea"},{"issue":"3","key":"bib4","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"issue":"3","key":"bib5","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.ajo.2014.11.028","article-title":"The association between dry eye disease and depression and anxiety in a large population-based study","volume":"159","author":"van der Vaart","year":"2015","journal-title":"Am J Ophthalmol"},{"issue":"2","key":"bib6","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.exer.2003.10.005","article-title":"Control of mucin production by ocular surface epithelial cells","volume":"78","author":"Dartt","year":"2004","journal-title":"Exp Eye Res"},{"issue":"5","key":"bib8","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/ACI.0b013e32830e6b04","article-title":"Functions of ocular surface mucins in health and disease","volume":"8","author":"Mantelli","year":"2008","journal-title":"Curr Opin Allergy Clin Immunol"},{"issue":"3","key":"bib9","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul Surf"},{"issue":"3","key":"bib10","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/j.1748-1716.2010.02225.x","article-title":"Purinergic signalling in epithelial ion transport: regulation of secretion and absorption","volume":"202","author":"Novak","year":"2011","journal-title":"Acta Physiol (Oxf)"},{"issue":"4","key":"bib11","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S0031-6997(24)01511-4","article-title":"International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors","volume":"53","author":"Fredholm","year":"2001","journal-title":"Pharmacol Rev"},{"issue":"3","key":"bib12","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s11302-016-9514-7","article-title":"A critical look at the function of the P2Y11 receptor","volume":"12","author":"Dreisig","year":"2016","journal-title":"Purinergic Signal"},{"issue":"4","key":"bib13","first-page":"1","article-title":"P2Y receptors (version 2019.4) in the IUPHAR\/BPS Guide to Pharmacology Database","volume":"2019","author":"Abbracchio","year":"2019","journal-title":"GtoPdb"},{"issue":"2","key":"bib14","first-page":"224","article-title":"Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor","volume":"50","author":"Nicholas","year":"1996","journal-title":"Mol Pharmacol"},{"issue":"2","key":"bib15","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1152\/physrev.00043.2006","article-title":"Physiology and pathophysiology of purinergic neurotransmission","volume":"87","author":"Burnstock","year":"2007","journal-title":"Physiol Rev"},{"issue":"3","key":"bib16","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul Surf"},{"key":"bib17","first-page":"327","article-title":"P2Y2 receptor agonists for the treatment of dry eye disease: a review","volume":"8","author":"Lau","year":"2014","journal-title":"Clin Ophthalmol"},{"issue":"3","key":"bib18","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1006\/exer.1998.0520","article-title":"Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva","volume":"67","author":"Jumblatt","year":"1998","journal-title":"Exp Eye Res"},{"issue":"4","key":"bib19","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1089\/108076803322279390","article-title":"P2Y2 receptor elicits PAS-positive glycoprotein secretion from rabbit conjunctival goblet cells in vivo","volume":"19","author":"Murakami","year":"2003","journal-title":"J Ocul Pharmacol Ther"},{"issue":"4","key":"bib20","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1089\/10807680260218524","article-title":"INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model","volume":"18","author":"Fujihara","year":"2002","journal-title":"J Ocul Pharmacol Ther"},{"issue":"1","key":"bib21","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/jcp.29846","article-title":"Maresin 1, a specialized proresolving mediator, stimulates intracellular [Ca2+] and secretion in conjunctival goblet cells","volume":"236","author":"Olsen","year":"2021","journal-title":"J Cell Physiol"},{"issue":"7","key":"bib22","first-page":"1455","article-title":"Isolation, characterization, and propagation of rat conjunctival goblet cells in vitro","volume":"42","author":"Shatos","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"bib23","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.jtos.2020.04.011","article-title":"RvE1 uses the LTB4 receptor BLT1 to increase [Ca2+]i and stimulate mucin secretion in cultured rat and human conjunctival goblet cells","volume":"18","author":"Yang","year":"2020","journal-title":"Ocul Surf"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jep.2016.03.025","article-title":"Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1\/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells","volume":"185","author":"Li","year":"2016","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"bib25","doi-asserted-by":"publisher","first-page":"C817","DOI":"10.1152\/ajpcell.00460.2009","article-title":"Role of purinergic signaling pathways in V-ATPase recruitment to apical membrane of acidifying epididymal clear cells","volume":"298","author":"Belleann\u00e9e","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"issue":"10","key":"bib26","doi-asserted-by":"publisher","first-page":"3410","DOI":"10.1167\/iovs.04-0141","article-title":"Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina","volume":"45","author":"Fries","year":"2004","journal-title":"Invest Ophthalmol Visual Sci"},{"issue":"7","key":"bib27","doi-asserted-by":"publisher","first-page":"8468","DOI":"10.1096\/fj.201802467R","article-title":"Resolvin D2 elevates cAMP to increase intracellular [Ca2+] and stimulate secretion from conjunctival goblet cells","volume":"33","author":"Botten","year":"2019","journal-title":"FASEB J"},{"issue":"11","key":"bib28","doi-asserted-by":"publisher","first-page":"6233","DOI":"10.3390\/ijms23116233","article-title":"Signaling pathways used by the specialized pro-resolving mediator maresin 2 regulate goblet cell function: comparison with maresin 1","volume":"23","author":"Olsen","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"11","key":"bib29","doi-asserted-by":"publisher","first-page":"6928","DOI":"10.1167\/iovs.12-10163","article-title":"Effect of histamine on Ca2+-dependent signaling pathways in rat conjunctival goblet cells","volume":"53","author":"Li","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"bib30","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.4049\/jimmunol.178.6.3912","article-title":"Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation","volume":"178","author":"Arita","year":"2007","journal-title":"J Immunol"},{"issue":"5","key":"bib31","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1111\/j.1476-5381.2009.00596.x","article-title":"A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain","volume":"159","author":"And\u00f3","year":"2010","journal-title":"Br J Pharmacol"},{"issue":"3","key":"bib32","doi-asserted-by":"publisher","first-page":"C830","DOI":"10.1152\/ajpcell.00291.2024","article-title":"Purinergic agonists increase [Ca2+]i in rat conjunctival goblet cells through ryanodine receptor type 3","volume":"327","author":"Fjaervoll","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"issue":"3","key":"bib33","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1007\/s11302-006-9008-0","article-title":"Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks","volume":"2","author":"Van Kolen","year":"2006","journal-title":"Purinergic Signal"},{"issue":"11","key":"bib34","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/0166-2236(89)90095-7","article-title":"Calcium-dependent and calcium-independent exocytosis","volume":"12","author":"Knight","year":"1989","journal-title":"Trends Neurosci"},{"issue":"2","key":"bib35","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11302-017-9556-5","article-title":"Hyperosmotic stress induces ATP release and changes in P2X7 receptor levels in human corneal and conjunctival epithelial cells","volume":"13","author":"Guzman-Aranguez","year":"2017","journal-title":"Purinergic Signal"},{"issue":"4","key":"bib36","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S0165-6147(97)90667-2","article-title":"Potential signalling roles for UTP and UDP: sources, regulation and release of uracil nucleotides","volume":"18","author":"Anderson","year":"1997","journal-title":"Trends Pharmacol Sci"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1002\/SERIES1767","article-title":"Agonists and antagonists for P2 receptors","volume":"276","author":"Jacobson","year":"2006","journal-title":"Novartis Found Symp"},{"issue":"19\u201320","key":"bib39","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.drudis.2012.06.010","article-title":"Subtleties in GPCR drug discovery: a medicinal chemistry perspective","volume":"17","author":"Fujioka","year":"2012","journal-title":"Drug Discov Today"},{"issue":"3","key":"bib41","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/sj.bjp.0701880","article-title":"Molecular cloning and characterization of rat P2Y4 nucleotide receptor","volume":"124","author":"Bogdanov","year":"1998","journal-title":"Br J Pharmacol"},{"issue":"2","key":"bib42","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/sj.bjp.0705043","article-title":"Coupling of the nucleotide P2Y4 receptor to neuronal ion channels","volume":"138","author":"Filippov","year":"2003","journal-title":"Br J Pharmacol"},{"issue":"8","key":"bib43","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s40265-015-0409-7","article-title":"Diquafosol ophthalmic solution 3%: a review of its use in dry eye","volume":"75","author":"Keating","year":"2015","journal-title":"Drugs"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.pharmthera.2018.04.002","article-title":"Tools and drugs for uracil nucleotide-activated P2Y receptors","volume":"190","author":"Rafehi","year":"2018","journal-title":"Pharmacol Ther"},{"issue":"5","key":"bib45","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.ceca.2015.08.004","article-title":"Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblasts","volume":"58","author":"Certal","year":"2015","journal-title":"Cell Calcium"},{"issue":"3","key":"bib46","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/sj.bjp.0706353","article-title":"The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion","volume":"146","author":"Ghanem","year":"2005","journal-title":"Br J Pharmacol"},{"issue":"4","key":"bib47","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1124\/mol.63.4.777","article-title":"Loss of nucleotide regulation of epithelial chloride transport in the jejunum of P2Y4-null mice","volume":"63","author":"Robaye","year":"2003","journal-title":"Mol Pharmacol"},{"issue":"1","key":"bib48","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/S0022-3565(24)35070-0","article-title":"Nucleotide stimulation of Cl\u2013 secretion in the pigmented rabbit conjunctiva","volume":"291","author":"Hosoya","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"issue":"18","key":"bib49","doi-asserted-by":"publisher","first-page":"5532","DOI":"10.1021\/jm060485n","article-title":"Structure\u2013activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor","volume":"49","author":"Besada","year":"2006","journal-title":"J Med Chem"},{"issue":"9","key":"bib50","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/glia.22693","article-title":"Inhibition of UDP\/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo","volume":"62","author":"Neher","year":"2014","journal-title":"Glia"},{"issue":"1","key":"bib51","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0022-3565(24)29509-4","article-title":"Cloning and functional characterization of two murine uridine nucleotide receptors reveal a potential target for correcting ion transport deficiency in cystic fibrosis gallbladder","volume":"297","author":"Lazarowski","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"bib52","doi-asserted-by":"publisher","first-page":"F419","DOI":"10.1152\/ajprenal.00075.2002","article-title":"Control of epithelial transport via luminal P2 receptors","volume":"284","author":"Leipziger","year":"2003","journal-title":"Am J Physiol Renal Physiol"},{"issue":"1\u20133","key":"bib53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ejphar.2007.10.040","article-title":"Hypotensive effect of UDP on intraocular pressure in rabbits","volume":"579","author":"Markovskaya","year":"2008","journal-title":"Eur J Pharmacol"},{"issue":"3","key":"bib54","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s11302-018-9614-7","article-title":"A promising drug candidate for the treatment of glaucoma based on a P2Y6-receptor agonist","volume":"14","author":"Jacob","year":"2018","journal-title":"Purinergic Signal"},{"issue":"3","key":"bib55","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.4049\/jimmunol.1003669","article-title":"The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation","volume":"187","author":"Giannattasio","year":"2011","journal-title":"J Immunol"},{"issue":"2","key":"bib56","doi-asserted-by":"publisher","first-page":"387","DOI":"10.4049\/jimmunol.1900916","article-title":"P2Y6 deficiency enhances dendritic cell-mediated Th1\/Th17 Differentiation and aggravates experimental autoimmune encephalomyelitis","volume":"205","author":"Li","year":"2020","journal-title":"J Immunol"},{"issue":"22","key":"bib57","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.2174\/0929867326666190725160621","article-title":"Tear film osmolarity, ocular surface disease and glaucoma: a review","volume":"26","author":"Fogagnolo","year":"2019","journal-title":"Curr Med Chem"},{"issue":"2","key":"bib58","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1097\/IJG.0000000000001713","article-title":"Assessment of ocular surface disease in glaucoma patients in Ghana","volume":"30","author":"Kobia-Acquah","year":"2021","journal-title":"J Glaucoma"},{"key":"bib7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/B978-0-12-374203-2.00053-1","article-title":"Conjunctival goblet cells","volume-title":"Encyclopedia of the Eye","author":"Hodges","year":"2010"},{"key":"bib37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-94-007-1217-1_1","article-title":"Nucleotide release by airway epithelia","volume-title":"Purinergic Regulation of Respiratory Diseases","author":"Lazarowski","year":"2011"},{"key":"bib40","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/B978-0-12-385526-8.00012-6","article-title":"Molecular pharmacology, physiology, and structure of the P2Y receptors","volume-title":"Pharmacology of Purine and Pyrimidine Receptors: Advances in Pharmacology","author":"von K\u00fcgelgen","year":"2011"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:06Z","timestamp":1791927126000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,2]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.1.46","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,21]]}}}