Basolateral surface

Figure 6, Polarized epithelial cells in culture. Epithelial cells in culture possess an apical surface with microvilli that faces the tissue culture medium (equivalent to the lumenal side of the cells in vivo), and a basolateral surface that faces the tissue culture dish (equivalent to the blood side of the cells in vivo).

The membrane surface facing the lumen is called the apical surface, and the membrane surface on the side facing blood is called the basolateral surface. The intestinal cells are joined at the tight junctions [63,75]. These junctions have pores that can allow small molecules (MW < 200 Da) to diffuse through in aqueous solution. In the jejunum, the pores are 7-9 A in size. In the ileum the junctions are tighter, and pores are 3-4 A in size (i.e., dimensions of mannitol) [63]. 

Glucose and galactose enter the absorptive cells by way of secondary active transport. Cotransport carrier molecules associated with the disaccharidases in the brush border transport the monosaccharide and a Na+ ion from the lumen of the small intestine into the absorptive cell. This process is referred to as "secondary" because the cotransport carriers operate passively and do not require energy. However, they do require a concentration gradient for the transport of Na+ ions into the cell. This gradient is established by the active transport of Na+ ions out of the absorptive cell at the basolateral surface. Fructose enters the absorptive cells by way of facilitated diffusion. All monosaccharide molecules exit the absorptive cells by way of facilitated diffusion and enter the blood capillaries. 

Active reabsorption occurs when the movement of a given substance across the luminal surface or the basolateral surface of the tubular epithelial cell requires energy. Substances that are actively reabsorbed from the tubule include glucose amino acids and Na+, POy3, and Ca++ ions. Three generalizations can be made regarding the tubular reabsorption of sodium, chloride, and water ... 

AQP4 is the major water facilitator in brain and is most concentrated in astrocyte endfeet, but AQP4 has not been found in neurons. It is localized to basolateral surfaces of ependymal cells and along the entire plasma-lemma of astrocytes, including processes that ensheath... 

However, not all proteins proceed directly to their eventual destination. Some proteins relocate from one plasma membrane compartment to another by means of trans-cytosis. Transcytosis involves endocytosis of selected proteins in one membrane compartment, followed by subsequent transport through early endosomes to recycling endosomes and finally translocation to a different membrane compartment, for example from the apical to the basolateral surfaces. Sorting at the TGN and endo-some recycling steps appear to have a primary role in the steady state distribution of proteins in different plasma membrane domains [47], However, selective retention of proteins at the plasma membrane by scaffolding proteins or selective removal may also contribute to normal distributions. Finally, microtubule-motor regulatory mechanisms have been discovered that might explain the specific delivery of membrane proteins to discrete plasma membrane domains [48]. 

Several symport proteins have been identified in the luminal and basolateral surfaces of the proximal tubule cells, each with a specific transport function. For example, mechanisms exist for transport of (i) neutral amino acids, except glycine, (ii) glycine alone, (iii) acidic amino acids (glutamate and aspartate), (iv) basic amino acids... 

As primary cultures of enterocytes fail to form a polarized epithelial monolayer and therefore, do not display an apical and basolateral surface, continuously growing (tumor) cell cultures can be used to investigate the permeation and... 

The taste cells are situated in the lingual epithelium with the apical membrane exposed to the mucosal surface of the oral cavity and the basal surface in contact with the nerve [interstitial fluid] [FIGURE 10]. Within the basolateral surface are the nerves which respond to the chemestiietic stimulants, i.e. direct nerve stimulation. The microvilli at the apical membrane contain receptor proteins which respond to sweeteners, some bitters and possibly coolants. The olfactory cells are bipolar neurons with dendritic ends containing cilia exposed to the surface and axons linked to the brain, where they synapse in the olfactory bulb. The transfer of information from this initial stimulus-receptor interaction to the brain processing centers involves chentical transduction steps in the membrane and within the receptor cells. The potential chemical interactions at the cell membrane and within the cell are schematically outlined in FIGURE 10. 

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

These transporters can be responsible for the toxicity of some xenobiotics. For example, the drug cephaloridine is toxic to the kidney as a result of accumulation in the proximal tubular cells, which form the cortex of the kidney. The drug is a substrate for OAT-1 on the basolateral surface and hence is transported into the proximal tubular cells. However, the transport out of these cells from the apical surface into the lumen of the tubule is restricted, probably because of the cationic group on the molecule (Fig. 7.34). The toxicity of cephaloridine is modulated by chemicals that inhibit the OAT-1 and cation transporters. The similar drug cephalothin is not concentrated in the cells and is not nephrotoxic (Table 3.5). See chapter 7 for more details. 

ATP-dependent ABC transporter family. However, it is atypical because it also contains a regulated chloride channel) In secretory epithelia of intestines, pancreas, lungs, sweat glands, and kidneys Cl enters epithelial cells through their basolateral surfaces using an Na+ + K+ + 2 Cl cotransporter and exits the cells through their apical surfaces using the CFTR channel. Absorptive epithelia also contain both the cotransporter and the CFTR channel, but Cl flows into the cells from the exterior surface, and the distribution of the cotransporter and CFTR between basolateral and apical surfaces is opposite to that in secretory cells.1... 

Figure 32-2 A pair of epithelial cells of Drosophila. The apical surface (top), e.g., of epithelial cells of the gut, faces the external surface, while the basolateral surface (bottom) binds to a basal membrane. Adheren junctions (AJ) and septate junctions (SJ) are shown between the cells. From Peifer and Tepass.84 Drawing by S. Whitfield.

The cells lining the lumen of the intestine are polarized, that is they have two distinct sides or domains which have different lipid and protein compositions. The apical or brush border membrane facing the lumen is highly folded into microvilli to increase the surface area available for the absorption of nutrients. The rest of the plasma membrane, the basolateral surface, is in contact with neighboring cells and the blood capillaries (Fig. 5). Movement between adjacent epithelial cells is prevented by the formation of tight junctions around the cells near the apical domain. Thus any nutrient molecules in the lumen of the intestine have to pass through the cytosol of the epithelial cell in order to enter the blood. 

Ito K, Suzuki H, Horie T, et al. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm Res 2005 22 1559-1577. 

Epithelial cells are cells covering the body surface and bounding cavities, e.g. the gut or kidney tubules. They are bound together laterally by tight junctions to form sheets of cells and their apical and basolateral surfaces differ in composition and are kept apart by the tight junctions. They have the ability to transport solutes across the cell sheet from the apical surface. Of course, in culture a single epithelial cell cannot exhibit these properties but as the cells divide they form stable clusters of tightly associated cells and monolayers of such cells do show polarity. This is most easily achieved in serum-free, hormonally defined medium ( 5.8) when differentiated... 

Epithelial cells normally exhibit polarity (Chapter 2) and this is generally not obvious when they are attached to an impermeable plastic surface. Millipore and Costar each produce inserts for 6-well and 24-well tissue culture trays (Fig. 3.2b) which allow the cells to attach to a semi-permeable membrane and to contact the medium on both apical and basolateral surfaces. The medium inside the insert (apical surface) does not mix with the medium in the well outside the insert and Costar s Transwell is designed to allow sampling of the two compartments with the insert in place. 

Fig. 5.1 Pathogenesis of Salmonella Typhimurium and Salmonella Typhi. Upon ingestion, Salmonella travel to the small intestine. The bacteria invade Microfold (M) cells and other intestinal epithelial cells through the apical surface to cause infection. (A). Salmonella Typhimurium remains localized in the small intestine and induces an inflammatory host immune response, resulting in bacterial clearance from immunocompetent individuals. (B). Salmonella Typhi escapes from intestinal epithelial cells at the basolateral surface of the intestinal epithelium, enters phagocytes, and evades the host innate immune response, resulting in systemic infection...

Another possibility is that certain drugs, of appropriate partition coefficients, would preferentially remain within the lipid bilayer of the plasma membrane, rather than partitioning out into the cell cytoplasm. Such moieties could thus diffuse along the lipid bilayer of the membrane, down the side of the cell (rather than through it), emerging finally at the basolateral surface of the cell. However this scenario is limited by the fact that the lipid membrane constitutes a minute proportion of the available surface area of the cell also cell junctions can act as diffusion barriers within the lipid bilayer of the plasma membrane. 

Fig. 3.1 Parietal cell in its resting and secreting state with the receptors for stimulation (ACh, H) and inhibition (EGF,SST,EP3) of acid secretion on its basolateral surface.

Bicarbonate ion (production catalysed by carbonic anhydrase) exits the cell on the basolateral surface, in exchange for chloride. The outflow of hicarhonate into hlood results in a slight alkalinity of the blood, known as the alkaline tide . 

Chloride ions enter the crypt epithelial cell by co-transport with sodium and potassium sodium is pumped back out via sodium pumps and potassium is exported via a number of channels on the basolateral surface. 

Shipitsin, M., and Feig, L.A. (2004). RalA but not RalB enhances polarized delivery of membrane proteins to the basolateral surface of epithelial cells. Mol Cell Biol 24 5746-5756. 

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