Vesicles, Pinocytotic

Endocytosis involves the ceUular uptake of exogenous molecules or complexes inside plasma membrane-derived vesicles. This process can be divided into two major categories (1) adsorptive or phagocytic uptake of particles that have been bound to the membrane surface and (2) fluid or pinocytotic uptake, in which the particle enters the cell as part of the fluid phase. The solute within the vesicle is released intracellularly, possibly through lysosomal digestion of the vesicle membrane or by intermembrane fusion (Fig. 3.4). 

The superficial two to three cell layers of the corneal and conjunctival epithelium are the main barrier for the permeation of topically applied compounds. In this rate-limiting cell layer, the transcellular permeation is dictated by the lipophilicity of the cell membrane whereas the paracellular permeation is limited by the paracellular pore size and density. Vesicular penetration (e.g., receptor- or endocytosis-mediated) of macromolecules across surface epithelium is possible [33], However, the proposed mechanism is energy consuming (e.g., incorporation into pinocytotic vesicles and phagosomes) and thus more feasible in cell lines with abundant intracellular energy sources like corneal endothelium and RPE [34-37]. 

The pharmacokinetics of PVP is well understood as a result of this agent s experimental use to determine the properties of pores in biological membranes. PVP molecules can readily penetrate hydrophilic pores in membranes if they are small enough, and they are also taken up by pinocytotic vesicles. Apparently, PVP is not detectably bound to membrane surfaces and hence does not provide long-lasting viscosity enhancement beyond the normal residence time in the tears. 

In the heart, the lead salt has been found to be deposited along the plasma membrane and sarcotubular system of muscle cells, and precipitation was enhanced by adrenaline, glucagon and F. In contrast, histamine caused particularly intense staining at the plasma membrane and the membrane of the pinocytotic vesicles of endothelial cell capillaries. This raises the possibility that cyclic AMP formed in endothelial cells of the coronary capillaries under the influence of histamine may affect cardiac cells, thereby acting as a local hormone. 

One of the mechanisms of active reabsorption is endocytosis. Fluid phase endocytosis consists of the incorporation of fluid and solutes in vesicles formed at the base of the brush border membrane of the proximal tubular cells (Figure 1). A more efficient absorptive endocytosis involves first binding of a drug, such as the cationic aminoglycoside and/or may be cadmium [30, 31], to a carrier (phosphatidyhnositol) located in the luminal membrane of the wall of the pinocytotic vesicle occurs followed by endocytosis and lysosomal fusion [32, 33]. 

Giurgea-Marin L,Toubeau G, Laurent G, Heuson-Stiennon JA,Tulkens PM, Impairment of lysosome-pinocytotic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses, Toxicol AppI Pharmacol, 1986,86 271-85. 

Entry of drugs into the cerebrospinal fluid (CSF) and extracellular space of the central nervous system (CNS) is relatively restricted. The endothelial cells of the CNS have tight junctions and do not have intercellular pores and pinocytotic vesicles. 

In addition to the blood-brain barrier, two other barrier layers limit and regulate molecular exchange at the interface between the blood and the neural tissue and its fiuid spaces the choroid plexus epithelium between blood and ventricular CSF and the arachnoid epithelium between blood and subarachnoid CSF. These CNS barriers perform a number of functions such as the ionic homeostasis, the restriction of small molecule permeation, the specific transport of small molecules required to enter or leave the brain, the restriction and regulation of large molecule traffic by reducing the fluid-phase endocytosis via pinocytotic vesicles, the separation of peripheral and central neurotransmitter pools, and the immune privilege [16]. 

Microvillus Fat droplets Pinocytotic vesicle Microvilli cutoff Terminal web... 

Scanning electron microscopic photographs of rabbit bronchial epithelium showed islands of lym-poepithehum varying from a few to a few hundred cells surrounded by a carpet of ciliated epithelium (Bienenstock and Johnston 1976). The flattened cells devoid of dlia consistently possessed small membrane projections, subsequently identified as microvilli by transmission electron microscopy. The lymphoepithelial cells generally contained mitochondria, but endoplasmic reticulum, pinocytotic vesicles, and phagosomes were not a feature. 

Fig. 302. An activated endothelial cell with pinocytotic vesicles and dilated cisternae of the endoplasmic reticulum from the region between the papillary muscles of the left ventricle (block 1278) from a rat (No. 9) treated for 7 consecutive days with intraperitoneal injection of 1.5 ml Tyrode s solution per kg body weight x day. On the last 4 days of experimentation the animal was exposed to an atmosphere containing only 5 % oxygen for 30 min. On August 4, 1976 half an hour after the last exposure under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Plate 3366...

This picture of the mechanism of uptake by the intestine is not easily reconciled with that obtained by morphological observations. This aspect has recently been reviewed by Palay and Revel (1964). Particulate fat in the intestinal lumen was shown to penetrate between the microvilli of the striated border and was then absorbed into the intestinal epithelial cells by passing into pinocytotic vesicles. These vesicles traverse the terminal web and the fat droplets were deposited within the lumen of the endoplasmic reticulum. They are transported in the Golgi apparatus and finally out of the cell along its lateral border. 

Perineurial cells have some features in common with endothelial cells, namely the ft quency of pinocytotic vesicles, the presence of a basement membrane and similar junctions between adjacent cells. Acute cadmium intoxication in mice did not, however, produce any degeneration of perineurial cells in nerves or peripheral ganglia and the perineurial diffusion barrier was intact also in cadmium-treated animals. ... 

The movement of compoimds from the circulating blood into the brain is strictly regulated by the brain capillary endothelial cells, which constitute the BBB. The importance of the BBB is not only in the passage of toxicants but also in therapeutic drugs and antidotes. Brain capillary endothelial cells are connected to each other by continuous tight jimctions and have a low number of pinocytotic vesicles. Several proteins (such as P-glycoproteins) and enzymes (such as monoamine oxidase, dopa decarboxylase, acetylcholinesterase, and others) are expressed by brain endothelial cells... 

Transmembrane movement of water in the absence of or against a limited osmotic gradient may theoretically occur by a number of mechanisms, since classical osmosis cannot be involved. Active transport of water has not been observed in vertebrates (Pappius, 1964). During pinocytosis (see above) a small quantity of the aqueous medium surrounding the membrane may be engulfed in the pinocytotic vesicle. The subsequent secretion of the water from the vesicle results in a net movement of the fluid from one side of the membrane to the other. 

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