Vectorial Transport

The SLC transporters mediate either drug uptake or efflux, whereas ABC transporters mediate only unidirectional efflux. Asymmetrical transport across a monolayer of polarized cells, such as the epithelial and endothelial cells of brain capillaries, is called vectorial transport (Figure 2-5). Vectorial transport is important in the efficient transfer of solutes across epithelial or endothelial barriers; it plays a major role in hepatobiliary and urinary excretion of drugs from the blood to the lumen and in the intestinal absorption of drugs and nutrients. In addition, efflux of drugs from the brain via brain endothelial cells and brain choroid plexus epithelial cells involves vectorial transport.

For lipophilic compounds with sufficient membrane permeability, ABC transporters alone can achieve vectorial transport by extruding their substrates to the outside of cells without the help of influx transporters. For relatively hydrophilic organic anions and cations, coordinated uptake and efflux transporters in the polarized plasma membranes are necessary to achieve the vectorial movement of solutes across an epithelium. Common substrates of coordinated transporters are transferred efficiently across the epithelial barrier. In the liver, a number of transporters with different substrate specificities are localized on the sinusoidal membrane (facing blood). These transporters are involved in the uptake of bile acids, amphipathic organic anions, and hydrophilic organic cations into hepatocytes. Similarly, ABC transporters on the canalicular membrane (facing bile) export such compounds into the bile. Overlapping substrate specificities between the uptake

Small Intestine: Liver: Kidney: Brain capillaries:

Small Intestine: Liver: Kidney: Brain capillaries:

FIGURE 2-5 Transepithelial or transendothelial flux. Transepithelial or transendothelial flux of drugs requires distinct transporters at the two surfaces of the epithelial or endothelial barriers. These are depicted diagrammatically for transport across the small intestine (absorption), the kidney and liver (elimination), and the brain capillaries that comprise the blood-brain barrier.

FIGURE 2-5 Transepithelial or transendothelial flux. Transepithelial or transendothelial flux of drugs requires distinct transporters at the two surfaces of the epithelial or endothelial barriers. These are depicted diagrammatically for transport across the small intestine (absorption), the kidney and liver (elimination), and the brain capillaries that comprise the blood-brain barrier.

transporters (Na+/taurocholate ┬┐┬╗transporting polypeptide [NTCP] and organic anion transporting polypeptide [OATP] family) and efflux transporters (BSEP, MRP2, P-glycoprotein, and BCRP) make the vectorial transport of organic anions highly efficient. Similar transport systems also are present in the intestine, renal tubules, and endothelial cells of the brain capillaries (Figure 2-5).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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