The Sodium/Iodide Symporter, Nitrate, and Dental Caries: A Perspective from a Review of the Literature

Nitrates have been used as an antimicrobial agent in foods for hundreds of years. As a result there is extensive literature on their mode of activity in the food sciences and other such diverse fields as gastroenterology, the pulmonary sciences, and cancer research but minimal research exists in the dental sciences. This manuscript will describe how nitrate present in green leafy vegetables is absorbed and concentrated in saliva. Through the intervention of facultative anaerobes in the oral cavity inert nitrate is converted to nitrite which through acidification becomes a potent nitrosating agent. The sodium/iodide symporter is responsible for the transport of nitrate from serum to saliva and agents that inhibit this process, goitrogens, will be shown to have an impact on caries rates. It is the nitrosation of critical sulfhydryl groups in glycolytic enzymes and carrier molecules that is responsible for the suppression of acid production and therefore the reduced cariogenicity of lactic acid bacteria. The difficulty in identifying nitrites behavior as an anticariogenic agent may stem from its cyclic nature due to its reliance on dietary intake. ______________________________________________________________________________ The sodium/iodide symporter,NIS, is a glycoprotein comprised of 618 amino acids.(1,2,3). It has the ability to concentrate iodide in thyroid cells, thyrocytes, against its electrochemical gradient by a factor of from 20 to 40 with respect to plasma, noted as T/P or T/S, thyroid to serum.(4,5). Two Na+ ions are transported with each anion and the energy released by the translocation down its electrochemical gradient is coupled to the transport of iodide uphill against its electochemical and concentration gradient. The energy needed for this process is derived from Na+/K+ ATPase.(1,5,6). The iodide is incorporated into the thyroid hormones T3, triiodotyrosine, and T4, thyroxine, in a process termed organification. The NIS is present not only in the thyroid but also a number of extrathyroidal tissues. These include the salivary glands, gastric mucosa, lactating mammary glands, chroid plexus, placenta, and kidney tubules.(1,4,7). All these tissues exhibit a number of similarities which include, 1) the ability to concentrate iodide by a factor of 20 to 40, 2) antagonistic inhibition of this concentrating mechanism by anions such as thiocyanate, SCN, perchlorate, ClO4, nitrate, NO3, and selenocyanate, SeCN, and 3) concentration of a number of anions other than iodide.(1). TSH, thyroid stimulating hormone, produced in the pituitary gland serves as a regulator by stimulating NIS gene and protein activity in thyrocytes which increases iodide uptake by the thyroid gland.(3). An important difference between the thyroid and salivary glands is that TSH has no impact on the activity of the salivary glands.(4,7,8,9). The function of the thyroid, whether it is hypothyroid, euthyroid, or hyperthyroid, also appears to have no influence on the salivary NIS in its anion transporting capabilities.(10). In addition, non-thyroidal tissues do not have the ability to produce T3 or T4. Also the salivary glands can concentrate thiocyanate by a factor of 20 unlike the thyroid where it is oxidized.(1,11). In spite of these differences the close association of the