Rationale: The entero-salivary circulation of inorganic nitrate (NO3-) involves the absorption of dietary nitrate in the gut and active uptake from blood by the salivary glands, leading to a 20-25-fold concentration in saliva. This recycling process is crucial for the nitrate-nitrite-nitric oxide (NO) pathway, which helps maintaining NO signaling in mammals. While the exact uptake mechanisms are unclear, sialin (encoded by the SLC17A5 gene) has been suggested to play a key role. Interestingly, studies from the 1950s indicate that nitrate transport in the salivary glands competes with iodide (I-). This prompted us to explore the role of the sodium/iodide symporter (NIS) in salivary nitrate uptake.
Method and results: Our database analysis revealed that the SLC5A5 gene (encoding NIS) and its protein are expressed at higher levels than SLC17A5 in the human salivary gland. Next, we expressed SLC5A5 in Xenopus Laevis oocytes and its functionality using electrophysiology. We could detect ion influx induced by nitrate, indicating nitrate transport. We also observed increased levels of nitrate in SLC5A5-injected oocytes and in human salivary gland cells overexpressing SLC5A5, after incubation with nitrate. Finally, to test the competition between nitrate and iodide in vivo, saliva samples were collected from patients receiving high doses of intravenous iodine (I2) contrast medium, a procedure known to generate considerable levels of circulating I-. We observed a marked decrease in salivary nitrate following the administration of contrast medium, indicating competition for salivary transport.
Conclusion: Our findings suggest that NIS is mediating salivary gland uptake and concentration of nitrate in saliva.
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