Cellular transport

In an oligonucleotide having n backbone linkages, this gives rise to 2 isomers that vary in their mechanism of action, cellular transport, as well as pharmacokinetics (53). Some of the most frequently encountered backbone modifications are Hsted in Table 1. 

The rate of side-chain cleavage of sterols is limited by the low solubiUty of substrates and products and thek low transport rates to and from cells. Cyclodextrins have been used to increase the solubiUties of these compounds and to assist in thek cellular transport. Cyclodextrins increase the rate and selectivity of side-chain cleavage of both cholesterol and P-sitosterol with no effect on cell growth. Optimal conditions have resulted in enhancement of molar yields of androsta-l,4-diene-3,17-dione (92) from 35—40% to >80% in the presence of cyclodextrins (120,145,146,155). 

If initial solute uptake rate is determined from intestinal tissue incubated in drug solution, uptake must be normalized for intestinal tissue weight. Alternative capacity normalizations are required for vesicular or cellular uptake of solute (see Section VII). Cellular transport parameters can be defined either in terms of kinetic rate-time constants or in terms of concentration normalized flux [Eq. (5)]. Relationships between kinetic and transport descriptions can be made on the basis of information on solute transport distances. Note that division of Eq. (11) or (12) by transport distance defines a transport resistance of reciprocal permeability (conductance). 

Cho MJ, DP Thompson, CT Cramer, T Vidmar, JF Scieszka. (1989). The Madin-Darby canine kidney (MDCK) epithelial cell monolayer as a model cellular transport barrier. Pharm Res 6 71-77. 

Brat SV, Williams GM. 1982. Hepatocyte-mediated production of sister chromatid exchange in cocultured cells by acrylonitrile Evidence for extra cellular transport of a stable reactive intermediate. Cancer Lett 17 213-216. 

It should be mentioned that the placental villous fragments can be used to measure uptake into the syncytiotrophoblast layer but they cannot be used for trans-cellular transport studies. If the transporter is expressed in the microvillous border membrane, the effects of various factors on transporter function can be determined. Another disadvantage is that the villous fragments may be heterogenous in composition and hence, uptake experiments may not be reflective of syncytiotrophoblast uptake alone. 

Kolhe, P, Khandare, J., Pillai, O., Kannan, S., Lieh-Lai, M., Kannan, R.M., Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload. Biomaterials 27, 660-669 (2006). 

Figure 1 The mode of action for bacterial AB-type exotoxins. AB-toxins are enzymes that modify specific substrate molecules in the cytosol of eukaryotic cells. Besides the enzyme domain (A-domain), AB-toxins have a binding/translocation domain (B-domain) that specifically interacts with a cell-surface receptor and facilitates internalization of the toxin into cellular transport vesicles, such as endosomes. In many cases, the B-domain mediates translocation of the A-domain into the cytosol by pore formation in cellular membranes. By following receptor-mediated endocytosis, AB-type toxins exploit normal vesicle traffic pathways into cells. One type of toxin escapes from early acidified endosomes (EE) into the cytosol, thus they are referred to as short-trip-toxins . In contrast, the long-trip-toxins take a retrograde route from early endosomes (EE) through late endosomes (LE), trans-Golgi network (TGN), and Golgi apparatus into the endoplasmic reticulum (ER) from where the A-domains translocate into the cytosol to modify specific substrates.

A report on the inhibitory effect of wheat-genn agglutinin on cellular transport may be relevant to this study, as this lectin binds to 2-aeet-amido-2-deoxy-D-glucose present in the same, L-asparagine-linked class of oligosaccharide that is affected by tunicamycin.549... 

The composition of the extracellular compartment is kept constant by the cooperation of the cellular transport systems with various transport systems which are located in epithelial layers connecting the organism with its environment (Table 1). Examples are the epithelia of the intestine, the kidney and of various glands. It is their function to establish a relatively constant concentration of the respective solutes... 

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