SODIUM/IODIDE SYMPORTER-NIS Abundant and Important in Gastric Mucosa
ABSTRACT Background: Iodine is essential for development and growth as a constituent in thyroid hormones. Biological mechanisms for iodide uptake and concentration are very important, espe-cially as iodine is a relatively scarce element. Active iodide transport into thyroid fol-licular cells is mediated by the sodium/iodide symporter (NIS), powered by Na+/K+-ATPase. NIS is expressed also in extra thyroidal tissues, most abundantly in gastric mucosa - the focus of this thesis. Cellular localisation of NIS: NIS expression was found basolaterally in gastric mucosal surface cells of several mammals including man, basolaterally in salivary gland ducts and apicolaterally in rat bile ducts. Weak NIS immunoreactivity was found basolaterally also in duodenal mucosal surface cells. Findings in gastric mucosa and salivary glands were confirmed by in situ hybridisation. Gastric iodide transport Considerable secretion of iodide from the bloodstream into the stomach, but negligi-ble uptake from the stomach, was shown in vivo and in vitro in rat using 125I as marker. In the Ussing-chamber in vitro system both the competitive NIS-inhibitor sodium perchlorate (NaClO4) and the Na+/K+-ATPase-inhibitor ouabain attenuated gastric iodide transport from serosal to mucosal side, proving that gastric iodide se-cretion is, to a large extent, mediated by NIS. NIS in MNNG-induced tumours: Gastric cancer was chemically induced in rats by the administration of N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in the drinking water. Multiple microadenomas as well as large adenomas were found in the stomachs of all MNNG-treated rats. The surface epithelium of gastric adenomas was NIS immunoreactive, but staining was less intense than in normal mucosa. In addition, almost all of the MNNG-treated animals displayed either large papillary cystadenomas in the liver, found to express NIS with varying staining intensity, and/or infiltrating carcinomas of Brunner’s glands, which did not express NIS. Conclusions: • NIS is abundantly expressed in gastric mucosa and also expressed in salivary gland and bile duct epithelium. • Iodide secretion into the gastric lumen is mediated by NIS. There are several theo-ries as to the function of this transport including mediating recirculation of io-dide, as well as securing presence of iodide in the stomach for antimicrobial or an-tioxidative purposes. • MNNG-induced tumours in gastric mucosa and bile ducts all express NIS, which might make radioiodine an aid in treatment and diagnosis of these cancer types.
Basic Medicine, Clinical Medicine, Ussing chamber, MNNG, gastric iodide secretion, ouabain, gastric cancer, sodium perchlorate, gastric NIS, bile duct cancer, Sodium/iodide symporter
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Lund University, Faculty of Medicine, Department of Clinical Medical Science Malmö, Section for Otorhinolaryngology