{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:12:43Z","timestamp":1779199963834,"version":"3.51.4"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,6]]},"abstract":"\n Psychiatric patients treated with lithium (Li\n +<\/jats:sup>\n ) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li\n +<\/jats:sup>\n -induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li\n +<\/jats:sup>\n inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6\n \u2013\/\u2013<\/jats:sup>\n ) mice and potentially novel connecting tubule\/principal cell\u2013specific AC6 knockout (AC6\n loxloxCre<\/jats:sup>\n ) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls. Dietary Li\n +<\/jats:sup>\n administration increased water intake and reduced urine osmolality in control, AC6\n \u2013\/\u2013<\/jats:sup>\n , and AC6\n loxloxCre<\/jats:sup>\n mice. Consistent with AC6\n \u2013\/\u2013<\/jats:sup>\n mice, medullary AQP2 and pS256-AQP2 abundances were lower in AC6\n loxloxCre<\/jats:sup>\n mice compared with controls under standard conditions, and levels were further reduced after Li\n +<\/jats:sup>\n administration. AC6\n loxloxCre<\/jats:sup>\n and control mice had a similar increase in the numbers of proliferating cell nuclear antigen\u2013positive cells in response to Li\n +<\/jats:sup>\n . However, AC6\n loxloxCre<\/jats:sup>\n mice had a higher number of H\n +<\/jats:sup>\n -ATPase B1 subunit\u2013positive cells under standard conditions and after Li\n +<\/jats:sup>\n administration. Collectively, AC6 has a minor role in Li-NDI development but may be important for determining the intercalated cell\u2013to\u2013principal cell ratio.\n <\/jats:p>","DOI":"10.1172\/jci.insight.91042","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T22:24:53Z","timestamp":1491517493000},"source":"Crossref","is-referenced-by-count":24,"title":["Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus"],"prefix":"10.1172","volume":"2","author":[{"given":"S\u00f8ren Brandt","family":"Poulsen","sequence":"first","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark."},{"name":"VA San Diego Healthcare System, San Diego, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina B\u00f8gelund","family":"Kristensen","sequence":"additional","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus, 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