Target cells, uptake

The intracellular signaltransduction of ofi-adrenoceptors is effectuated by a G-protein-dependent activation of the phospholipase C. This enzyme cleaves phosphatidylinositol, a phospholipid present in cell membranes, into inositol-1,4-5-triphosphate (IP3) and diacylglycerol (DAG). IP3 is a strong inductor of intracellular calcium release which leads to an increase of smooth muscle tone or the liberation of hormones stored in vesicles. Noradrenaline which is released by exocytosis, spreads by diffusion only. Only a small fraction of the total amount of the transmitter released will actually reach the postsynaptic membrane and bind to its specific receptors. Another fraction escapes the synapic cleft by diffusion and is finally enzymatically degraded in the interstitial fluid. Another fraction is taken up postsynaptically and metabolized enzymatically by the target cells (uptake 2). By far most of the transmitter (90%) is actively taken up by the releasing neuron itself (uptake 1 or neuronal re-uptake). In the... 

Receptor Targeted Cell Uptake Studies on the BBB In Vitro... 

Distribution Vector fraction target cell uptake... 

Data on the association of chemical exposures and adverse reproductive outcomes in humans, however, are equivocal and often controversial. Some studies indicate that chemical exposures are associated with infertility, spontaneous abortion, or reproductive cancer in women. In contrast, other studies indicate that there is no association between chemical exposure and adverse reproductive outcomes. The reasons for such ambiguous findings in human studies are un known, but likely include the fact that many studies are limited by multiple con founders, inadequate methodology, inappropriate end points, and small sample size. The mechanisms by which chemicals alter reproductive functions in all spe cies are complex and may involve hormonal and/or immune disruption, deoxyri bonucleic acid (DNA) adduct formation, altered cellular proliferation, or inappropriate cellular death. There is very little information on the effects of metabolism and intracellular binding proteins on target cell uptake of endocrine disrupters. 

Proteins embedded in the shell of lipoproteins. They serve as scaffold for assembly of the lipoprotein particle in the endoplasmic reticulum. In addition, they control metabolism of lipoproteins in the circulation by interaction with enzymes such as lipases. Finally, apolipoproteins determine cellular uptake of the particles by interaction with specific lipoprotein receptors expressed on the surface of target cells. 

A highly stable and shielded polyplex should circulate in the blood stream without undesired interactions until it reaches the target cell. At that location, specific interactions with the cell surface should trigger intracellular uptake. While lipid membrane interaction is undesired at the cell surface, it should happen subsequently within the endosomal vesicle and mediate polyplex delivery into the cytosol. During or after intracellular transport to the site of action, the polyplex stability should be weakened to an extent that the nucleic acid is accessible to exert its function. 

C arbohydrate-remodelled gluco cerebro sidase Enzymatic removal of sialic acid caps exposes mannose residues, triggering selective product uptake by macrophages (the target cell type) 12... 

Lp(a) will also be targeted to uptake by macrophages by the scavenger receptor pathway. Macrophages, turning into foam cells, play an important role in plaque formation. 

The DNA or cDNA library is then introduced into a preparation of bacterial host cells. Usually, the first host selected is a laboratory strain of E. coli which has been grown and pretreated with inorganic salts to make uptake of DNA easier. The ability to take up foreign DNA is called competence, cells which have been specially prepared for the purpose are called competent cells. Other methods to transfer DNA into cells include electroporation (application of an external electric field to permeabUize the cell wall), transfection (where a recombinant bacterial virus is used to transfer the DNA to the target cell) or ballistic methods (by using DNA-coated particle projectiles). The last method has been used to introduce foreign DNA into plant cells and mammalian cells. 

To bridge this gap, liposomal transfection efficiency can be dramatically enhanced by the inclusion of peptides into the complex without increasing immunogenicity. Peptides can be selected to assist lipofection at each key stage of the process complex formation, cell targeting and uptake, endosomal disruption, and nuclear targeting. The purpose of this chapter is... 

In principle, liposomes can enter (target) cells through different pathways by direct fusion of liposomes and the plasma membrane (1) or by an endo-cytic uptake mechanism. Other liposome-cell interactions that have been described in the literature are absorption, phospholipid and protein exchange, and cell-induced leakage of liposome contents (2,3). 

Once specific liver uptake is established, the intrahepatic distribution needs to be addressed. The importance of this issue is exemplified by the apparently high uptake of untargeted Dexa by the liver. Dexa itself was taken up exclusively by the hepatocytes, whereas targeted Dexa was taken up by SECs and KCs [152], the target cells for anti-inflammatory therapy. 

These distribution studies show that fiver slices can be used to assess the level of uptake of a drug into the target cells in both healthy and diseased human fiver. Isolation of non-... 

Although such receptors often provide mechanisms for internalization followed by intracellular transport to compartments where degradation takes place, the rates of these processes can be markedly different in various cell types. In some cases only external binding occurs and consequently, the microclimate of the cell membrane at which local release of the drug from the carrier takes place, should provide sufficient driving force to ensure uptake of the drug into the target cell. 

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