Extracellular medium

The development of amphipathic fluorescent dyes that label endocytic vesicles has permitted the study of endo-cytosis in nerve terminals in real time [25,26], The probe FM1-43 equilibrates between the aqueous phase and the membrane but is not membrane-permeating. The plasmalemma becomes fluorescent (Fig. 10-8). Upon endocytosis, the labeled membrane is internalized. When removed from the extracellular medium, the dye is retained by the endocytic vesicles but lost from the plasmalemma. Endocytic vesicles are transformed into synaptic vesicles containing FM1-43. Importantly, recycled synaptic vesicles lose the probe upon exocytosis. 

Figure 3. Monitoring the uptake of Li+ into human erythrocytes after incubation in media containing 2 mM Li+ using 7Li NMR spectroscopy. The signals corresponding to the intra-, and extracellular Li+ are separated by the presence of the paramagnetic shift reagent, Dy(P30io)2, the extracellular medium [34].

Figure 4.10. Dose-relationships for histamine release from rat mast cells induced by a variety of peptides [99], No calcium was added to the extracellular medium. Each point is the mean of two or more determinations A, poly(L-lysine) (molecular weight 30.000-70,000) , succinylated poly(L-lysine) (molecular weight 30,000-70f)00) V, [n-Phe7 )SP , fD-Prcr2, D-Phe7, D-Trpv]SP, u , SP/ A, eledoisin-related peptide , eledoisin O, N-terminal tetrapeptide of substance P.

Mammalian cells maintain a lower concentration of Na+ (around 12 mM) and a higher concentration of K+ (around 140 mM) than in the surrounding extracellular medium (respectively, 145 and 4 mM). The system (Na+-K+)-ATPase, which maintains high intracellular K+ and low intracellular Na+, is localized in the plasma membrane, and belongs to the family of P-type ATPases. Other members of the family in eukaryotes are the sarcoplasmic reticulum and plasma membrane Ca2+ ATPases and, in plants, the H+-ATPases. The overall reaction catalysed is ... 

Several mechanistic models have also been proposed to elucidate how the P-gp transporter translocates substrates across cellular membranes. In the vacuum cleaner model, which seems the most probable, the compounds partition into the membrane bilayer and then P-gp extracts the substrates from the inner (cytosolic) membrane leaflet and releases them through a protein channel into the extracellular medium (Figure 16.1) [7,14,17]. 

Figure 16.1 Schematic representation of a vacuum cleaner model drug partitions into the membrane bilayer, flips across the lipid core, accesses the TMDs from the inner membrane leaflet and is released through a protein channel into the extracellular medium.

When deficient in iron, bacteria and fungi produce and excrete to the extracellular medium low molecular weight, specific iron-carrier molecules, called siderophores. These siderophores bind ferric ions, to form soluble complexes. The complexed ferric ions are transported into the cell through high-affinity and energy-dependent receptor proteins located on the outer membrane. In Gram-negative bacteria, such as E. coli, the most studied system, siderophore-iron complexes are transported initially to the periplasm. 

Fig. I. Endocytic pathways used by cells to internalize soluble macromolecules [25] fluid-phase pinocytosis (1), adsorptive pinocytosis (2), and receptor-mediated endocytosis (pinocytosis) (6). Each of these processes involves a formation of a sealed vesicle formed from the plasma membrane which encloses part of the extracellular medium. The internalization of a polymer-drug conjugate (P-D), and targeted polymer-drug conjugate ( => —P-D) is shown. Other abbreviations — = cell surface receptor/antigen 1 = clathrin molecule X = lysosomal enzyme. Fluid-phase pinocytosis (1) and adsorptive pinocytosis (2) are nonspecific processes which direct the macromolecule into the lysosomal compartment of the cell. Once P-D is internalized, whether by (1) or (2), the resulting endosome (3) is ultimately fused with a primary lysosome (4) forming a secondary lysosome (5). In the latter compartment P-D is in contact with several types of lysosomal enzymes. The membrane of (5) is impermeable to macromolecules. Consequently, the structure of P-D may be designed in such...

In endocrine signaling the hormone is synthesized in specific signaling, or endocrine, cells and exported via exocytosis into the extracellular medium (e.g. blood or lymphatic fluid in animals). The hormone is then distributed throughout the entire body via the circulatory system so that remote regions of an organism can be reached. 

Fig. 3.5. Endocrine, paracrine and autocrine signal transduction, a) endocrine signal transduction the hormone is formed in the specialized endocrine tissue, released into the extracellular medium and transported via the circulatory system to the target cells, b) paracrine signal transduction the hormone reaches the target cell, which is found in close juxtaposition to the hormone producing cell, via diffusion, c) autocrine signal transduction the hormone acts on the same ceU type as the one in which it is produced.

Bacteria can target proteins to their inner or outer membranes, to the periplasmic space between these membranes, or to the extracellular medium. They use signal sequences at the amino terminus of the proteins (Fig. 

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