Pinocytic capture

Compared with phagocytosis, fluid-phase pinocytic capture of molecules is relatively slower, being directly proportional to the concentration of macromolecules in the extracellular fluid. It is also dependent on the size of macromolecules in general, lower molar mass fractions are captured faster than the higher molar mass fractions. The magnitude of the rate of capture by adsorptive pinocytosis is higher than that by fluid-phase pinocytosis and relates to the nature of substrate-membrane interactions. 

Duncan R, Cable HC, Rejmanove P, et al. Tyrosinamide residues enhance pinocytic capture of N-(2-hydroxypropyl)methacrylamide copolymers. Biochim Biophys Acta 1984 799 1-8. 

Duncan et al. have shown that the incorporation of phenolic residues into macromolecules increases their rate of pinocytic capture. The incorporation of 20 % tyramine residues into poly[a,P-(N-hydroxyethyl)-DL-aspartamide)] greatly in-... 

Progressive accumulation of radioactivity by cells is not a reflection of the rate of pinocytic capture if the substrate is digested intrarallularly, thus releasing low molecular weight labelled products which can diffuse back out of the cell. 

Renal filtration and pinocytic capture are two processes which effect the distribution of a polymer in the body. There are many processes such as penetration through capillary walls about which we have only little or no information at all. Some macromolecules may be transported from one cell type to another, either by direct transfer or exocytic release followed by pinocytic iqttake by a different cell type. It has been shown that polymers such as PVP which can persist in cells for long periods are also slowly excreted by the body. I-labelled PVP captured by liver is slowly transported via the bile canaliculi and gall bladder to the intestine and excreted in the faeces... 

Efficiency of pinocytic capture can be greatly enhanced if substrates adsorb to the internalizing plasma membrane.Physiologically this phenomenon is utilized by cells to ensure that they capture efficiently those macromolecules they require. Some macro-... 

R. Duncan, H. C. Cable, J. Strohalm and J. Kopecek, Pinocytic capture and exocytosis of rat immunoglobulin IgG-N-(2-hydrox) ropyl)methacrylamide copolymer conjugates by rat visceral yolk sacs cultured in vitro, Biosci. Rep., 6, 869-877 (1986). 

Pinocytosis seems to be the main if not the only way in which a synthetic water-soluble polymer can enter an intact cell As almost all mammalian cells have developed a pinocytic function through which they can take many important metabolites they all can also capture synthetic polymers together with the surrounding fluid. The rate of polymer uptake by a particular cell is determined by the polymer concentration in the surounding medium and by the size and the rate of formation of pinocytic vesicles by the cell... 

From the preceding considerations it is obvious that the pinocytic uptake of a polymer by cells is affected by fundamental parameters sudi as overall charge, hydro-phobicity, and not least molecular weight. These parameters are crucial in the design of efficient drug delivery systems. Much more work is still required in this area to elucidate the mechanism of capture of the polymers which are believed to be valuable drug delivery systems. In the necessary experiments several factors require special consideration, for example ... 

As mentioned above, HPMA copolymers containing approximately 2% oligopeptidyl side-chains have no affinity for the plasma membrane and enter cells by fluid-phase pinocytosis. Increasing the hydrophobicity of macromolecules appears to enhance, non-specifically, their rate of capture by rat visceral yolk sacs and we have shown that incorporation of 20% tyramine residues into the synthetic polymer poly-a-3"N(2-hydroxyethyl) -D,-L- aspartamide greatly enhances its rate of uptake by this tissue.More recently we have found that incorporation of tyrosine residues (approximately 18%) into HPMA oligopeptidyl side-chains produces the same results (Table 4). The existence of a correlation between the percentage tyrosine in the molecule and the rate of pinocytic uptake indicates that synthetic polymers can be designed in such a way as to control their non-specific affinity for membranes. 

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