Apical luminal surface

It was postulated that the aqueous pores are available to all molecular species, both ionic and non-ionic, while the lipoidal pathway is accessible only to un-ionised species. In addition, Ho and co-workers introduced the concept of the aqueous boundary layer (ABL) [9, 10], The ABL is considered a stagnant water layer adjacent to the apical membrane surface that is created by incomplete mixing of luminal contents near the intestinal cell surface. The influence of drug structure on permeability in these domains will be different for example ABL permeability (Paq) is inversely related to solute size, whereas membrane permeability (Pm) is dependent on both size and charge. Using this model, the apparent permeability coefficient (Papp) through the biomembrane may therefore be expressed as a function of the resistance of the ABL and... 

The apical membrane of a polarised cell is that part of the plasma membrane that forms its luminal surface, particularly so in the case of epithelial and endothehal cells. The basolateral membrane of a polarised cell refers to that part of the plasma membrane that forms its basal and lateral surfaces. Proteins are free to move from the basal to lateral surfaces, but not to the apical surface tight junctions, which join epithehal cells near their apical surfaces, prevent migration of proteins to the apical surface. The apical surface is therefore distinct from the basal/lateral surfaces. 

A system that more closely resembles the in vivo state is the porous membrane system. Because cells can receive nutrient from both sides of the membrane, the cell layer has an active basal and apical (or luminal) surface that allows the selective uptake and transport of nutrients and secreted products. A variety of biological functions can now be studied, such as active transport, better differentiation and co-culture of different cell types (Pitt Gabriels, 1986 Millipore, 1990 Halleux Schneider, 1991). 

Interestingly, the distribution of BCRP in normal tissues is similar to that of P-glycoprotein. High levels of BCRP expression were detected in the human placenta syncytiotrophoblast plasma membrane, facing the maternal bloodstream, in the canalicular membrane of the liver hepatocytes, the apical membrane of the epithelium in the small and large intestines, in the ducts and lobules of the breast, and in the luminal surface of brain capillaries.260 261 In addition, significant amounts of... 

Because bicarbonate is a small ion, it is freely filtered at the glomerulus. The bicarbonate load delivered to the nephron is approximately 4,500 mEq/day. To maintain acid-base balance, this entire filtered load must be reabsorbed. Bicarbonate reabsorption occurs primarily in the proximal tubule (Fig. 51-1). In the mbular lumen, filtered bicarbonate combines with hydrogen ion secreted by the apical Na+-H+-exchanger to form carbonic acid. The carbonic acid is rapidly broken down to CO2 and water by carbonic anhydrase located on the luminal surface of the brush border membrane. The CO2 then diffuses into the proximal tubular cell, where it reforms carbonic acid in the presence of intracellular carbonic anhydrase. The carbonic acid dissociates to form hydrogen ion, that can again be secreted into the tubular lumen, and bicarbonate that exits the cell across the basolateral membrane and enters the peritubular capillary. 

P-gp is constitutively expressed in nearly all barrier tissues. Techniques involving Northern blots (37) or Western blots with monoclonal antibodies such as C219 (38) and MRK 16 (39) have been used extensively to determine the tissue distribution of P-gp. It is expressed in adrenal cortex, kidney, liver, intestine, and pancreas endothelial cells at blood-tissue barriers, namely, the CNS, the testis, and in the papillary dermis (3,4,38,40,41). P-gp displays specific subcellular localization in cells with a polarized excretion or absorption function. More specifically, P-gp is found at the apical (AP) canalicular surface of hepatocytes, in the AP membrane of the columnar epithelial cells of colon and jejunum, and the AP brush border of the renal proximal tubule epithelium (3,4,40 1-2). In endothelial cells, P-gp is located in the luminal membrane (4,43). 

Their main function is the sampling and presentation of antigens to the luminal tissue, In comparison with absorptive ceils, they have a diminished glycocalyx. They also have short, irregular microfolds at the apical surface,... 

Macromolecules, such as proteins and peptides, are taken up by polarized epithelial cells by random pinocytosis, i.e., sampling of luminal fluid containing such molecules into apical early endosomes (AEE) as shown for MDCK cells in vitro (Leung et al. 2000). Further intracellular sorting is depicted in general terms in Fig. 3.3. Recycling to the apical surface or transcytosis is then mediated... 

In the toad urinary bladder, an experimental model of the mammalian collecting tubule, addition of hthium to the mucosal surface (but not to the serosal surface) markedly inhibited both basal and arginine vasopressin-stimulated water flow [50]. The concentration of mucosal lithium used in these studies (10 mEq/L) was comparable to or even lower than that usually found in the urine of patients on well-controlled lithium therapy (that is, 10 to 40 mEq/L) [63] Fernandez et al. [53] confirmed the inhibitory effect of lithium on water flow in toad urinary bladders exposed only submaximal concentrations of arginine vasopressin. Inhibition of cyclic adenosine monophosphate-stimulated water flow when lithium (2 mEq/L) was applied to the serosal surface of the toad bladder was reported in one study. Such an effect of lithium, when applied to the serosal surface has, to our knowledge, not been found by any other investigators. As herein discussed, the bulk of evidence supports the notion that the action of lithium on water transport is the result of its cell uptake from the luminal (apical) surface of the collecting tubule. 

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