Endothelial cell membrane

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

Although the absence of paracellular transport across the BBB impedes the entry of small hydrophilic compounds into the brain, low-molecular-weight lipophilic substances may pass through the endothelial cell membranes and cytosol by passive diffusion [7]. While this physical barrier cannot protect the brain against chemicals, the metabolic barrier formed by the enzymes from the endothelial cell cytosol may transform these chemicals. Compounds transported through the BBB by carrier-mediated systems may also be metabolized. Thus, l-DOPA is transported through the BBB and then decarboxylated to dopamine by the aromatic amino acid decarboxylase [7]. 

Like the glucose carrier, the carriers for large neutral amino acids, the so-called L-system - now designated LAT - are present at both sides of the endothelial cell membranes and transport at least 10 essential amino acids. The L-transporter at the BBB has a much higher transport capacity than those in other tissues. Its marked preference for phenylalanine analogs explains why the anticancer drugs melphalan and d,l-NAM-7 are transported by the L-system, as is the L-Dopa used to treat Parkinson s disease [42]. 

The oft-touted argument against a physiological role for HbSNO is that even if it does form in RBCs, the Hb-bound NO has to make quite a journey to get to smooth muscle cells it must first cross the RBC plasma membrane, then the RBC free zone (Liao et al., 1999), then cross the endothelial cell membranes twice and finally go through the smooth muscle membrane. Why would nature adopt such a convoluted route when the endothelial cells next to the smooth muscle cells are producing membrane-diffusable NO ... 

Detailed photochemical studies of RBS and RRS have revealed that the photolysis of RRS produces RBS and NO quantitatively (Scheme 5.6) and the RBS produced undergoes further photodecomposition to generate NO and iron (III) [165, 168]. RBS has been tested as an NO delivery drug to the vascular and brain tissues by thermal as well as photochemical means [169, 170]. Due to the high solubilities in aprotic solvents, Roussin s salts are able to penetrate the endothelial cell membrane easily and deliver NO for hours [169]. RBS has been found to inhibit ADP-induced platelet aggregation [171] and Roussin s salts in general show a bacteriostatic effect, presumably due to the interaction of released NO and iron-sulfur proteins [172]. 

Most endothelial cell membranes are ordinarily impermeable to proteins. Transport across these barriers occurs only with the aid of receptor-mediated or other transport processes. However, many active sites (receptors) are located on cell surfaces and there is no need to permeate the cell. To achieve an adequate intracellular concentration, relatively large amounts of protein must be administered. Proteins administered by nonparenteral means and intended for systemic effects, such as intranasally and directly into the lungs. 

Similarly, drugs injected into the SC or IM space are separated from the blood compartment by the endothelial cells of the capillaries. From the interstitial space, such drug molecules must first diffuse toward and then partition into the endothelial cell membrane. After traversing these cells, the drugs must then partition on the luminal, or blood facing, side of these cells into the blood, which carries them away. By this dilution effect, the blood presents sink conditions, thus maintaining a maximal concentration gradient, dCm/dx, to drive diffusion toward the blood. 

Hajjar, K.A., 1993, Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J. Clin. Invest 91, 2873-2879. 

Endothelial cells have a well-developed endocytotic capacity [24, 25, 47], Several receptors at the endothelial cell membrane rapidly clear specific substances from the blood. These endocytotic receptors include the scavenger recep-... 

A. H. Stolpen, D. E. Golan, and J. S. Pober, Tumor necrosis factor and immune interferon act in concert to slow the lateral diffusion of proteins and lipids in human endothelial cell membranes, J. Cell Biol. 707 781-789 (1988). 

Preissner KT. Anticoagulant potential of endothelial cell membrane components. Haemostasis 1988 18271-273. 

Bovine adrenal capillary endothelial cells Membrane-based patterning of protein, BSA backfill 2000 [92]... 

Additionally, the blood-brain barrier can be overcome when molecules that are highly expressed by brain capillary endothelial cell membranes (e.g., transferrin) are targeted by specific antibodies as reported by Pardridge et al. 

Water moving from the blood into the brain through an intact BBB has to cross three membranes luminal and abluminal endothelial cell membranes, and the membrane of the astrocyte foot processes (Kimelberg, 2004 Tait et al., 2008). High density of AQP4 is present in the vascular-facing astrocytic membranes. Although... 

Carvalho, F.A., Graqa, L.M., Martins-Silva, J., Saldanha, C. (2005). Biochemical characterization of human umbilical vein endothelial cell membrane bound acetylcholinesterase. FEBS J. 111-. 5584-94. 

Nitric oxide is made in the endothelial cells of the blood vessels. However, NO does not provoke a change in these cells. The hormone, occurring at concentrations of 10-1000 nM, diffuses through the endothelial cell membrane and into nearby smooth muscle which encircles the blood vessel (Beckman and Koppenol, 1996). Once inside the muscle cell, NO binds to guanylate cyclase, and activates it. Guanylate cyclase catalyzes the conversion of GTP to cyclic GMP (cGMP), as shown here ... 

Horvat R et al (1986) Endothelial cell membranes contain podocalyxin—the major sialo-protein of visceral glomerular epithelial cells. J Cell Biol 102(2) 484-491... 

N. V. Ketis, R. L. Hoover, and M. J. Kamovsky. Isolation of bovine aortic endothelial cell membranes. Identification of membrane associated cytoskeletal proteins. J. Cell Biol. 725 162-171 (1986). 

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