Transcellular

Epithelial calcium channel 1 (ECaCl), synonym TRJPV5, is a member ofthe TRP family of ion channels, implicated in vitamin D-dependent transcellular Ca2+ transport in epithelial cells ofthe kidney, placenta and the intestine. 

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

TRPV5 and TRPV6, also known as the epithelial Ca2+ channel or ECaC (TRPV5) and Ca2+transporter 1 or Ca2+ transporter-like (TRPV6), are the only two Ca2+-selective TRP channels identified so far. They may function in vitamin D-dependent transcellular transport of Ca2+in kidney, intestine and placenta. TRPV6 is also expressed in pancreatic acinar cells, and in prostate cancer, but not in healthy prostate or in benign prostate hyperplasia. 

Sasaki M, Suzuki H, Aoki J, Ito K, Meier PJ and Sugiyama Y. Prediction of in vivo biliary clearance from the in vitro transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II monolayer expressing both rat organic anion transporting polypeptide 4 and multidrug resistance associated protein 2. Mol Pharmacol 2004 66 450-9. 

Figure 41-14. The transcellular movement of glucose in an intestinal cell. Glucose follows Na+ across the luminal epithelial membrane. The Na+ gradient that drives this symport is established by Na+ -K+ exchange, which occurs at the basal membrane facing the extra-ceiiuiarfiuid compartment. Glucose at high concentration within the ceii moves "downhill" into the extracel-iuiarfiuid by fadiitated diffusion (a uniport mechanism).

Fittipaldi A, Giacca M (2005) Transcellular protein transduction using the Tat protein of HIV-1. Adv Drug Deliv Rev 57 597-608... 

OITATE M, NAKAKI R, KOYABU N, TAKANAGA H, MATSUO H, OHTANI H, SAWADA Y (2001) TranSCellular transport of genistein, a soybean-derived isoflavone, across human colon carcinoma cell line (Caco-2). Biopharm Drug Dispos. 22 23-9. 

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. 

The pH-partition theory or nonionic permeability hypothesis was first described by Jacobs in 1940 [66]. According to this concept, only neutral, preferably nonpolar compounds are able to cross biological membranes. The transcellular permeability pH-profile is then essentially characterized by the membrane partition coefficient and the pKa of the compound. The simplest quantitative description of membrane permeation is given by ... 

Kelder et al. [19] have shown that PSA can be used to model oral absorption and brain penetration of drugs that are transported by the transcellular route. A good correlation was found between brain penetration and PSA (n=45, r=0.917). From analyzing a set of 2366 central nervous system (CNS) and non-CNS oral drugs that have reached at least phase 11 clinical trials it was concluded that orally active drugs that are transported passively by the transcellular route should have PSA< 120 Al In addition, different PSA distributions were found for CNS and non-CNS drugs. 

Sola, P., Godessart, N., Vila, L., Puig, L. and Moragas, J.M. (1992). Epidermal cell-polymorphonuclear leukocyte cooperation in the formation of leukotriene B4 by transcellular biosynthesis. J. Invest. Dermatol. 98, 333-339. 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

PAMPA is typically used to make a prediction of the passive, transcellular absorption of a compound. Compounds which may be absorbed by a paracellular mechanism or may be substrates for active transport (uptake or efflux) are usually better assessed in a cell based system. A combination of assays can be applied to gain a greater understanding of the permeability and transport properties of a compound. 

The transcellular fluid includes the viscous components of the peritoneum, pleural space, and pericardium, as well as the cerebrospinal fluid, joint space fluid, and the gastrointestinal (GI) digestive juices. Although the transcellular fluid normally accounts for about 1% of TBW, this amount can increase significantly during various illnesses favoring fluid collection in one of these spaces (e.g., pleural effusions or ascites in the peritoneum). The accumulation of fluid in the transcellular space is often referred to as third spacing. To review the calculations of the body fluid compartments in a representative patient, see Patient Encounter 1. 

Transcellular Transport of Protein—Polymer Conjugates in Cultured Epithelial Cells... 

SHEN ET AL. Transcellular Transport of Protein-Polymer Conjugates 119... 

Figure 3. Transcellular transport of HRP-S-PLL in filter-grown MDCK cell monolayers. Confluent MDCK monolayers in Transwells were treated at the basal compartment (closedsquares)or the apical compartment (open squares) with 3 pg/mL HRP-S-PLL conjugate.

Figure 5. Schematic illustration of the pathway involved in the transcellular transport of HRP-S-PLL.

Figure 6. Transcellular transport of HRP-SS-PDL in a filter-grown MDCK cell monolayer. HRP-SS-PDL was added to the apical medium (closed squares) or to the basal medium (open squares).

Most drugs appear to be absorbed in humans by passive diffusion (linear or first-order kinetics). The predominant pathway taken by most drugs is through the epithelial cell, the transcellular route. It is this route that requires the compound to have a reasonable K0/w... 

Fig. 9 Schematic representation depicting the movement of molecules from the absorbing (mucosal or apical) surface of the GIT to the basolateral membrane and from there to blood. (A) transcellular movement through the epithelial cell. (B) Paracellular transport via movement between epithelial cells. (Q Specialized carrier-mediated transport into the epithelial cell. (D) Carrier-mediated efflux transport of drug out of the epithelial cell. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

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