Extracellular space structure

Nicholson C, Sykova E (1998) Extracellular space structure revealed by diffusion analysis. Trends Neurosci 21 207-215... 

One of the key parameters for correlating molecular structure and chemical properties with bioavailability has been transcorneal flux or, alternatively, the corneal permeability coefficient. The epithelium has been modeled as a lipid barrier (possibly with a limited number of aqueous pores that, for this physical model, serve as the equivalent of the extracellular space in a more physiological description) and the stroma as an aqueous barrier (Fig. 11). The endothelium is very thin and porous compared with the epithelium [189] and often has been ignored in the analysis, although mathematically it can be included as part of the lipid barrier. Diffusion through bilayer membranes of various structures has been modeled for some time [202] and adapted to ophthalmic applications more recently [203,204]. For a series of molecules of similar size, it was shown that the permeability increases with octa-nol/water distribution (or partition) coefficient until a plateau is reached. Modeling of this type of data has led to the earlier statement that drugs need to be both... 

These loop-shaped terminations of the sheath at the node are called lateral loops. The loops form membrane complexes with the axolemma called transverse bands, whereas myelin in the internodal region is separated from the axon by an extracellular gap of periaxonal space. The transverse bands are helical structures that seal the myelin to the axolemma but provide, by spaces between them, a tortuous path from the extracellular space to the periaxonal space. 

The FhuA receptor of E. coli transports the hydroxamate-type siderophore ferrichrome (see Figure 9), the structural similar antibiotic albomycin and the antibiotic rifamycin CGP 4832. Likewise, FepA is the receptor for the catechol-type siderophore enterobactin. As monomeric proteins, both receptors consist of a hollow, elliptical-shaped, channel-like 22-stranded, antiparallel (3-barrel, which is formed by the large C-terminal domain. A number of strands extend far beyond the lipid bilayer into the extracellular space. The strands are connected sequentially using short turns on the periplasmic side, and long loops on the extracellular side of the barrel. 

An old hypothesis is based on the observations of Dahlen et al. (D3), who demonstrated that above a certain concentration in plasma, Lp(a) could bind to glycosaminoglycans in the arterial wall (B12). Colocalization of Lp(a) and fibrin on the arterial wall can lead to oxidative changes in the lipid moiety of Lp(a) and induce the formation of oxidatively modified cholesterol esters, which in turn can influence the interaction of Lp(a) and its receptors on macrophages. This process is promoted by the presence of calcium ions. Cushing (C14), Loscalzo (L22), and Rath (R3) reported a colocalization of undegraded Lp(a) and apo-Bl00 in the extracellular space of the arterial wall. In contrast to LDL, Lp(a) is a substrate for tissue transglutaminase and Factor XUIa and can be altered to products that readily interact with cell surface structures (B21). 

Following its uptake into the body, the drug is distributed in the blood (1) and through it to the various tissues of the body. Distribution may be restricted to the extracellular space (plasma volume plus interstitial space) (2) or may also extend into the intracellular space (3). Certain drugs may bind strongly to tissue structures, so that plasma concentrations fall significantly even before elimination has begun (4). 

The transfer of the action potential to the SR is made possible by transverse tubules (T tubules), which are open to the extracellular space and establish a close connection with the SR. There is a structure involved in the contact between the T tubule and the SR that was formerly known as the SR foot (it involves parts of the ryanodine receptor see p. 386). 

Extracellular Matrix A meshwork-hke substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in cultiu-e dishes adhere. [NIH]... 

Finally, Chap. 6 deals with the exploitation of biocatalysis in generating supramolecular polymers, a class of polymers where the monomers are connected via non-covalent bonds. This approach provides highly dynamic and reversible supramolecular structures, inspired by biological polymeric systems found in the intra- and extracellular space. A number of potential applications of enzymatic supramoleular polymerizations are discussed in the context of biomedicine and nanotechnology. 

In comparison to signaling pathways which utilize transmembrane receptors (see chapter 5, 8,11), signahng via nuclear receptors is of relatively simple structure. The pathways lead directly, with only a few participating protein components, from the extracellular space to the level of the DNA in the nucleus. Most important protein components of the signal pathway are known and well characterized. Nevertheless, we understand very little of the mechanism by which the activated receptors lead to a transcription initiation. This is due to the extreme complexity of transcription initiation in eucaryotes (see 1.2). Both the variety of proteins involved in the formation of a competent initiation complex, as well as the influence of chromatin structure, make it difficult to elucidate the exact function of nuclear receptors in transcription initiation. 

---