Carrier-mediated transport nature

On the other hand, several probe substrates of carrier-mediated transport systems in the small intestine have been reported to be not absorbed by carrier-mediated mechanism in the rat colon in situ. Those include L-carnitine [23], methotrexate [18], cephradine [18], and 5-fluorouracil [18], as substrates of the L-carnitine carrier, folate carrier, peptide carrier, and pyrimidine carrier, respectively (Table 3.3). It is based on the nonsaturable nature of their transport. Particularly, the apparent membrane permeabilities of L-carnitine and methotrexate are negligibly low, suggesting that these compounds are practically unabsorbable from the colon. In the case of 5-fluorouracil, Na+-independence of transport was observed in situ [18] and also in everted sacs in vitro in the colon [21], while its carrier in the small intestine is known to be Na+-dependent. Furthermore, for ascorbate and nicotinate, as described in everted sacs in vitro [21], and L-dopa, as described in situ [24], carrier-mediated transport cannot be observed in the rat colon. 

An example of RUI analysis method using [3H]adenosine is shown in Figure 14.3B. The RUI value of [3H]adenosine is greater than that of [3H]d-mannitol (used as a paracellular transport marker) and significantly reduced by 30% in the presence of 2 mM unlabeled adenosine and thymidine, while 2 mM cytidine has no effect. Thus, the nature of the inhibition shown by this approach confirms the carrier-mediated transport of adenosine from the blood to the retina across the BRB in vivo [27],... 

Drug absorption from the oral cavity occurs through the passive diffusion of the nonionized form from an aqueous phase to one that is lipid in nature. In addition, there is also evidence for the carrier-mediated transport of drugs, whereby the levo isomers, but not the dextro isomers, of many drugs are absorbed. 

This study shows that K. pneumoniae when growing under aerobic or semiaerobic conditions, transports NO3" into the cells. Therefore assimilatory or aerobic NOa" reduction probably occurs inside the cells. The observation that NO2" is transiently excreted into the mediiun from which it then disappears suggests the presence of both a NO2" export system (possibly a consequence of NO3" reduction by a membrane-associated enzyme) and a NO2" uptake system. The presence of a NO2" uptake capability may simply reflect the permeability of membranes to weak acids in the presence of a transmembrane pH gradient (19-23) or may indicate the presence of carrier-mediated transport systems. If the N02 uptake is carrier-mediated, the transient nature of the accumulation of N02 outside the cells suggests that uptake and/or reduction may be activated shortly after the cells are exposed to N03 . It may also be possible that simultaneous transport of nitrite across the cell membrane and reduction are mediated by one enzyme system. While we have not attempted to demonstrate a membrane-associated nitrite reductase, Jones and Garland (3) and Coleman et al. (22) have found such activities in other enteric bacteria. 

Apart from these intrinsic factors, due primarily to chiral nature of the skin components, extrinsic factors such as differences in physicochemical properties between enantiomers and racemate have been reported to cause stereoselective permeation, particularly with respect to individual optical isomers versus their racemates [38]. In addition to differences in the physicochemical properties, other extrinsic factors were also implicated in the enantioselective permeation across the skin including (1) the presence of chiral permeation enhancers [32,33,39], (2) the presence of stereoselective retardants in the donor vehicle [40], (3) differences in the hydrolysis rates of the prodrugs of the enantiomers in epidermis/dermis [23-25], and (4) carrier mediated transport [41]. 

The findings of the present investigation indicate that the K , value for hepatic taurocholate uptake significantly increases at birth in the rabbit. This observed increase in K , indicates that the overall efficiency of hepatic uptake of taurocholate decreases at birth. Conceptually, this observed change in can be attributed to two factors (a) alterations in the hepatocyte membrane to affect carrier conformation and mobility (b) structural modifications in the carrier protein. Recent studies by Benz et al. (1977) on the influence of membrane structure on carrier-mediated transport demonstrated that the translocation rate constant or K,n is strongly dependent on the nature of the membrane structure. 

Although there is a natural tendency toward equilibrium of the solute concentration on both sides of the membrane, such an equilibrium is rare in a living system, and selective permeability of the plasma membrane therefore assures the required distribution of metabolically important material inside and outside the cell. Kinetic studies of solute transport often permit characterization of the type of transmembrane movement involved (Neame and Richards, 1972). As outlined by Csaky (1965), a given substance can cross the cell membrane in several different ways free diffusion, diffusion through pores, pinocytosis, and carrier-mediated transport. 

The nature of the carrier represents an open question, and only its isolation and identification can provide an appropriate answer. Considering substrate specificity, which is characteristic for carrier-mediated transport, it is very likely that the substrate binding site is proteinaceous, because protein possesses selective behavior. This presumption... 

Because of its catalytic nature, a single antibody-enzyme conjugate would activate many molecules of the prodrug in question. Much of the active cytocidal agent released at the tumour surface would be taken up by the tumour cells via simple diffusion or carrier-mediated active transport. 

Because of the possible effects of active and carrier-mediated processes and metabolic biotransformation, the issue of tissue viability is important for in vitro buccal mucosal experiments. The barrier nature of the buccal mucosa resides in the upper layers of the epithelium, where unlike in the stratum corneum, the cells contain a variety of functional organelles [119, 122, 125, 150], and so tissue viability may be an important component of the barrier function of the tissue. Various methods have been employed to assess the viability of excised buccal mucosa, including measurement of biochemical markers, microscopic methods, and linearity of transport data [42], While biochemical methods, including measurement of adenosine 5 -triphosphate (ATP) levels and utilization of glucose, provide information on the metabolic activity of the tissue, this does not necessarily relate to the barrier function of the tissue. In excised rabbit buccal mucosa, levels of ATP were measured and found to decline by 40% in 6 h, and this correlated well with transmission electron microscopic evaluation of the tissue (intact superficial cells) [32], In addition, the permeability of a model peptide was unaltered up to 6 h postmortem, but at 8 h, a significant change in permeability was observed [32], These investigators therefore claimed that excised rabbit buccal mucosa could be used for diffusion studies for 6 h. 

If a drag is sufficiently similar to a substance naturally transported by a carrier-mediated system, the drag may also be transported by the same system. For example, the drags levodopa, methyldopa and... 

Carrier-Mediated Intestinal Transport. Various carrier mediated systems (transporters) are present at the intestinal brush border and basolateral membrane for theabsorption of specific ions and nutrients essential for the body. Many drugs are absorbed by these carriers because of the structural similarity to natural substrates. An intestinal transmembrane protein, P-Glycoprotein (F-Gp) appears to reduce apparent intestinal epithelial cell permeability from lumen to... 

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