{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:19:45Z","timestamp":1767374385719,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["Merit Review Program"],"award-info":[{"award-number":["Merit Review Program"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Therapeutic use of lithium in bipolar disorder is limited by the development of nephrogenic diabetes insipidus (NDI). We reported that pharmacological blockade of P2Y<jats:sub>12<\/jats:sub> receptor (R) with clopidogrel or prasugrel significantly ameliorated lithium\u2010induced NDI in rodents. Using mice genetically lacking P2Y<jats:sub>12<\/jats:sub>\u2010R we evaluated whether the observed amelioration is mediated through P2Y<jats:sub>12<\/jats:sub>\u2010R<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>P2ry12<jats:sup>\u2212\/\u2212<\/jats:sup> mouse line (C57\/BL6) was rederived from cryopreserved embryos of the knockout (KO) mice generated by Deltagen Inc. Syngeneic wild type (WT) mice obtained by heterozygous crossing were inbred. Groups of adult WT and KO mice were fed lithium\u2010added (40\u00a0mmol LiCl\/kg food) or regular diet, and euthanized after 2 or 4\u00a0weeks. Twenty\u2010four hour urine samples and terminal blood and kidney samples were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At both time points, lithium\u2010induced polyuria and decrease in aquaporin\u20102 (AQP2) protein abundance in the kidney medulla were less marked in KO vs WT mice. Immunofluorescence microscopy revealed that lithium\u2010induced alterations in the cellular disposition of AQP2 protein in the medullary collecting ducts of WT mice were blunted in KO mice. Serum lithium, sodium and osmolality were similar in both genotypes after lithium treatment. After 2\u00a0weeks, lithium induced marked increases in urinary excretion of Na, K, and arginine vasopressin in WT mice but not in KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, our data show that similar to pharmacological blockade, deletion of P2Y<jats:sub>12<\/jats:sub>\u2010R significantly ameliorates lithium\u2010induced NDI, without reducing serum lithium levels. Hence, targeting P2Y<jats:sub>12<\/jats:sub>\u2010R with currently available drugs in the market offers a novel and safer method for treating NDI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13191","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T19:28:12Z","timestamp":1537990092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic deletion of ADP\u2010activated P2Y<sub>12<\/sub> receptor ameliorates lithium\u2010induced nephrogenic diabetes insipidus in mice"],"prefix":"10.1111","volume":"225","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Utah Health Sciences Center Salt Lake City Utah"},{"name":"Nephrology Research, Department of Veterans Affairs Salt Lake City Health Care System Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenny 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Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel G.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Center on Aging University of Utah Health Sciences Center Salt Lake City Utah"},{"name":"Department of Neurobiology and Anatomy University of Utah Health Sciences Center Salt Lake City Utah"},{"name":"Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Salt Lake City Health Care System Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8232-9827","authenticated-orcid":false,"given":"Bellamkonda K.","family":"Kishore","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Utah Health Sciences Center Salt Lake City Utah"},{"name":"Nephrology Research, Department of Veterans Affairs Salt Lake City Health Care System Salt Lake City Utah"},{"name":"Center on Aging University of Utah Health Sciences 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