Cotransport, membrane

Sodium-dependent glucose cotransporters (SGLT) are located on small-intestine and kidney brush-border membranes. SGLT1, SGLT2, and SGLT3 are... 

The bumetanide-sensitive Na+, K+, 2CF cotransporter (NKCC) mediates the electroneutral uptake of chloride across epithelial cell membranes and is found in both absorptive and secretory epithelia (airways, salivary gland). NKCC exists in two isoforms, the secretory isoform NKCC1, and the absorptive isoform NKCC. 

NKCC is a heavily glycosylated protein with 12 putative membrane-spanning regions. Thirty percent of the sodium that is filtered by renal glomeruli is reabsorbed by Na-K-2C1 cotransport in the ascending limb of Henle in the nephron. Na-K-2C1 cotransport is a target of all loop diuretics. 

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

In many epithelia Cl is transported transcellularly. Cl is taken up by secondary or tertiary active processes such as Na 2Cl K -cotransport, Na Cl -cotransport, HCOJ-Cl -exchange and other systems across one cell membrane and leaves the epithelial cell across the other membrane via Cl -channels. The driving force for Cl -exit is provided by the Cl -uptake mechanism. The Cl -activity, unlike that in excitable cells, is clearly above the Nernst potential [15,16], and the driving force for Cl -exit amounts to some 2(f-40mV. 

Figure 10 Schematic of cotransporters and countertransporters (or exchangers) in en-terocyte mucosal and basolateral membranes.

Both secondary active transport and positive cooperativity effects enhance carrier-mediated solute flux, in contrast to negative cooperativity and inhibition phenomena, which depress this flux. Most secondary active transport in intestinal epithelia is driven by transmembrane ion gradients in which an inorganic cation is cotransported with the solute (usually a nutrient or inorganic anion). Carriers which translocate more than one solute species in the same direction across the membrane are referred to as cotransporters. Carriers which translocate different solutes in opposite directions across the membrane are called countertransporters or exchangers (Figs. 10 and 11). 

Possible driving forces for solute flux can be enumerated as a linear combination of gradient contributions [Eq. (20)] to solute potential across the membrane barrier (see Part I of this volume). These transbarrier gradients include chemical potential (concentration gradient-driven diffusion), hydrostatic potential (pressure gradient-driven convection), electrical potential (ion gradient-driven cotransport), osmotic potential (osmotic pressure-driven convection), and chemical potential modified by chemical or biochemical reaction. 

Several types of cells are equipped with carrier proteins to transport essential nutrients such as glucose and amino acids that cannot cross the plasma membrane freely because of their hydrophilicity. Intestinal and renal epithelia have long been known to possess specialized Na+ cotransport processes for glucose [205], amino acids [206], and di- and tripeptides [207],... 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Takanaga, H., et al. Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane. J. Pharm. Pharmacol. 1996, 48, 1073-1077. 

Kramer, W., et al. Substrate specificity of the ileal and the hepatic Na(+)/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters. J. Lipid Res. 1999, 40, 1604-1617. 

Adenosine and inosine can be transported across cell membranes in either direction, facilitated by a membrane-associated nucleoside transport protein. Concentrative transporters have also been identified. Messenger RNA for a pyrimidine-selective Na+-nucleoside cotransporter (rCNTl) and a purine-selective Na+-nucleoside cotransporter (rCNT2) are found throughout the rat brain. Most degradation of adenosine is intracellular, as evidenced by the fact that inhibitors of adenosine transport, such as dipyridamole, increase interstitial levels of adenosine. Dipyridamole is used clinically to elevate adenosine in coronary arteries and produce coronary vasodilation. In high doses, dipyridamole can accentuate adenosine-receptor-mediated actions in the CNS, resulting in sedation and sleep, anticonvulsant effects, decreased locomotor activity and decreased neuronal activity. 

In the case of metal ions present as anionic complexes in the donor phase, solvating or ion-pairing extractants can be used as carriers. Here the metal ions and counterions are cotransported across the membrane from the donor to the acceptor phase. By using a complexing or reducing agent in... 

The resorption process is facilitated by the large inner surface of the intestine, with its brush-border cells. Lipophilic molecules penetrate the plasma membrane of the mucosal cells by simple diffusion, whereas polar molecules require transporters (facilitated diffusion see p. 218). In many cases, carrier-mediated cotransport with Na"" ions can be observed. In this case, the difference in the concentration of the sodium ions (high in the intestinal lumen and low in the mucosal cells) drives the import of nutrients against a concentration gradient (secondary active transport see p. 220). Failure of carrier systems in the gastrointestinal tract can result in diseases. 

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