{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:28:36Z","timestamp":1761863316690},"reference-count":28,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2014,5,15]]},"abstract":"<jats:p>Water-handling epithelia are sensitive to the osmotic environment. In this study, the effects of a hypo-osmotic challenge on carbachol (CCh)-induced fluid secretion was investigated using an ex vivo submandibular gland perfusion technique and intracellular pH and Ca<jats:sup>2+<\/jats:sup>measurements. The osmolality of the perfusion solution was altered to examine the response of the gland to a hypotonic challenge. The flow rate was increased by 34% with a 30% hypotonic solution (225 mosmol\/kgH<jats:sub>2<\/jats:sub>O), although the Ca<jats:sup>2+<\/jats:sup>response was unchanged. The lowering of the external Cl<jats:sup>\u2212<\/jats:sup>by 50% abolished this increase in the 30% hypotonic solution. Furthermore, bumetanide, an inhibitor of the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter (NKCC1), completely inhibited the fluid secretion increase caused by the 30% hypotonic solution, and both the total amount of fluid and the flow rate were identical to those of the isotonic solution. This finding was confirmed by measuring the NKCC1 bumetanide-dependent NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>transport; Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>transport was upregulated &gt;40% by a 30% hypotonic challenge. Therefore, the increase in CCh-induced fluid secretion in response to hypotonic conditions can be attributed, to a large extent, to the specific activation of the NKCC1.<\/jats:p>","DOI":"10.1152\/ajprenal.00709.2012","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T04:09:24Z","timestamp":1394683764000},"page":"F1155-F1160","source":"Crossref","is-referenced-by-count":11,"title":["Na<sup>+<\/sup>-K<sup>+<\/sup>-2Cl<sup>\u2212<\/sup>cotransporter-mediated fluid secretion increases under hypotonic osmolarity in the mouse submandibular salivary gland"],"prefix":"10.1152","volume":"306","author":[{"given":"Manami","family":"Kidokoro","sequence":"first","affiliation":[{"name":"Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu City, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuji","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Department of Oral 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