Sodium symporters

The melibiose carrier MelB of E. coli is a well-studied sodium symport system. This carrier is of special interest, because it can also use protons or lithium ions for cotransport. The projection structure of MelB has been solved at 8 A resolution [107]. The 12 TM helices are arranged in an asymmetrical pattern similar to the previously solved structure of NhaA, which, however, follows an antiport mechanism (Na+ ions out of the cell and H+ into the cell). 

Fig. 1). These monoamine transporters belong to the SLC6 gene family of Na -Cl"-coupled neurotransmitter transporters that is also referred to as the neurotransmitter sodium symporter (NSS) family (Chen et al., 2004). In addition to the monoamine transporters, the NSS family includes subfamilies of transporters for GABA, amino acids, creatine, and the osmolytes betaine and taurine (Chen et al., 2004). 

A low or even a moderate single dose of iodide causes no or only a minor, reduction of hormone production in a normal thyroid. An excessive single dose of iodide leads, via inhibition of the thyroid peroxidase (TPO) mediated iodination (the Wolff-ChaikofF effect), to a transient decrease of intrathyroidal hormone concentration. This was first demonstrated by Wolff and Chaikoff (1949). When high plasma levels of iodide are sustained by repeated iodine administration, the inhibiting effect disappears and normal organic iodine levels in the thyroid are restored, with a decrease in thyroid sodium symporter, as demonstrated by Eng et al. (1999). This effect was demonstrated by Haydl and Waldhausl (1975) in the course of health resort treatments administering iodine-containing mineral waters. 

The monosaccharides that are released by this enzyme action are absorbed into the enterocytes via sodium-dependent cotransporters (also called sodium symporters). From the enterocytes, the monosaccharides enter the portal vein and are taken up by the liver where they are processed further in ways described in this chapter. 

Amino acids, dipeptides, and some tripeptides are transported from the lumen of the small intestine through the membrane of the absorptive cells of the brash border, where the peptides are hydrolyzed to amino acids. Transport of peptides and amino acids is active and analogous to glucose transport in the intestine i.e., they are transported by specific protein carriers, together with Na across the cell membrane and they are called sodium symporters. 

The difference in the hydrogen ion electrochemical potential, formed in bacteria similarly as in mitochondria, can be used not only for synthesis of ATP but also for the electrogenic (connected with net charge transfer) symport of sugars and amino acids, for the electroneutral symport of some anions and for the sodium ion/hydrogen ion antiport, which, for example, maintains a low Na+ activity in the cells of the bacterium Escherichia coli. 

Thiazide diuretics such as chlorothiazide act on the distal tubule, a portion of the tubule that is permeable to sodium. The mechanism of action of these diuretics involves inhibition of NaCl reabsorption by blocking the Na+, CL symporter in the luminal membrane. The thiazide diuretics are only moderately effective due to the location of their site of action. Approximately 90% of the filtered Na+ ions have already been reabsorbed when the filtrate reaches the distal tubule. These drugs may be used for treatment of edema associated with heart, liver, and renal disease. Thiazide diuretics are also widely used for the treatment of hypertension. 

EGER targeting was also used for systemic delivery of pDNA expressing the sodium iodide symporter (NIS) gene to liver cancer cells, followed by administration of radioactive isotope iodine-131, which accumulates in the tumor by NIS-mediated uptake in radiotherapeutic doses [227]. 

The recovery of neurotransmitters from synaptic clefts and their storage in cytoplasmic vesicles is accomplished by the tandem actions of the secondary transporters in plasma and vesicular membranes. Sodium-dependent symporters mediate neurotransmitter reuptake from synaptic clefts into neurons and glia, whereas proton-dependent antiporters concentrate neurotransmitters from neuronal cytoplasm into synaptic vesicles (Fig. 5-13). 

SODIUM-DEPENDENT SYMPORTERS IN THE PLASMA MEMBRANES CLEAR GLUTAMATE FROM THE EXTRACELLULAR SPACE 286... 

Amino add reabsorption in the renal tubules Amino acids are small, easily filtered molecules. Efficient reabsorption mechanisms are vital to conserve amino acids which are metabolically valuable resources. Transport of individual amino acids and small peptides is symport carrier mediated mechanisms in which sodium is co-transported. The process is indirectly ATP dependent because Na is returned to the lumen of the nephron by the sodium pump , Na+/K+ dependent ATPase. 

Reizer, J., Reizer, A. and Saier Jr., M. (1994) A functional superfamily of sodium / solute symporters. Blochim BiophysActa 1197, 133-166. 

Breast milk During lactation human mammary tissue expresses the sodium iodide symporter [260], and thus significant transfer of perchlorate into human milk is likely. The presence of micrograms per liter concentrations of perchlorate in milk collected fi om US women [233] confirms lactation as a relevant perchlorate excretion path. If lactating women are secreting perchlorate in milk, then urine-based estimates of total perchlorate exposure for these individuals are likely to be lower than actual [242]. 

De Groef B, Decallonne BR, Van der Geyten S, Darras VM, Bouillon R (2006) Perchlorate versus other environmental sodium/iodide symporter inhibitors potential thyroid-related health effects. Eur J Endocrinol 155 17-25... 

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

Bizhanova A, Kopp P (2009) The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 150 1084—1090... 

Dohan O, De la Vieja A, Carrasco N (2000) Molecular study of the sodium-iodide symporter (NIS) a new field in thyroidology. Trends Endocrinol Metab 11 99-105... 

The perchlorate ion of potassium perchlorate, KCIO4, is a competitive inhibitor of thyroidal 1 transport via the Sodium Iodide Symporter (NIS).This drug can cause fatal aplastic anemia and gastric ulcers and is now rarely used. If administered with careful supervision, in limited low doses and for only brief periods, serious toxic effects can be avoided. The compound is especially effective in treating iodine-induced hyperthyroidism, which may occur, for example, in patients treated with the antiar-rhythmic compound amiodarone. Perchlorate ion can also be used in a diagnostic test of 1 incorporation into Tg, the so-called perchlorate discharge test. 

---