Intestines membrane transport

In summary, Caco-2 cells studies strongly suggest that carotenoids interact with each other at the level of cellular uptake by the enterocyte. This phenomenon has been explained by the fact that the uptake of several carotenoids involves, at least in part, the same intestinal membrane transporter the scavenger receptor class B type ISR-BI (Reboul et al. 2005, van Bennekum et al. 2005, Moussa et al. 2008). 

Anderle P, Huang Y, Sadee W (2004) Intestinal membrane transport of drugs and nutrients Genomics of membrane transporters using expression microarrays. Eur J Pharm Sci 21 17-24. 

One of the possible applications directly related to multivalent ligand-receptor interactions will be the design of polymeric inhibitors which specifically bind receptors existing on cellular membranes to inhibit the uptake of biological substrates via the receptors. For example, there are many kinds of intestinal membrane transporters for... 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Precellular solute ionization dictates membrane permeability dependence on mucosal pH. Therefore, lumenal or cellular events that affect mucosal microclimate pH may alter the membrane transport of ionizable solutes. The mucosal microclimate pH is defined by a region in the neighborhood of the mucosal membrane in which pH is lower than in the lumenal fluid. This is the result of proton secretion by the enterocytes, for which outward diffusion is slowed by intestinal mucus. (In fact, mucosal secretion of any ion coupled with mucus-restricted diffusion will provide an ionic microclimate.) Important differences in solute transport between experimental systems may be due to differences in intestinal ions and mucus secretion. It might be anticipated that microclimate pH effects would be less pronounced in epithelial cell culture (devoid of goblet cells) transport studies than in whole intestinal tissue. 

JS Patton. Is the intestinal membrane bilayer freely permeable to lipophilic molecules In F Alvarado, CH van Os, eds. Ion Gradient-Coupled Transport. INSERM Symposium No. 26. Amsterdam Elsevier Science, 1986, pp 33-36. 

Transport across the small intestinal membrane is passive. 

Several attempts have been made to estimate the dose required in humans in relation to a drug s potency, and to put this into the context of solubility and permeability for an optimal oral drug [2, 3]. A relatively simple example of this is where a 1.0 mg kg-1 dose is required in humans, then 52 pg mL"1 solubility is needed if the permeability is intermediate (20-80%) [3]. This solubility corresponds approximately to 100 pM of a compound with a MW of 400 g mol-1. Most screening activities for permeability determinations in, e.g., Caco-2, are made at a concentration of 10 pM or lower due to solubility restrictions. The first implication of this is that the required potency for these compounds needs to correspond to a dose of <0.1 mg kg-1 in humans if the drug should be considered orally active. Another implication would be the influence of carrier-mediated transport (uptake or efflux), which is more evident at low concentrations. This could result in low permeability coefficients for compounds interacting with efflux transporters at the intestinal membrane and which could either be saturated or of no clinical relevance at higher concentrations or doses. 

Assessing the effect of the intestinal metabolism in the Peff as a membrane transport rate parameter is a methodological issue [7, 26, 34, 35, 49]. An evaluation of its influence has to include a study to establish which enzyme(s) is (are) involved and the site of metabolism in relation to the site of the measurements. Intracellular metabolism in the enterocyte, for instance by CYP 3A4 and di- and tri-... 

Ungell, A. L., Nyiander, S., Bergstrand, S., Sjoberg, A., Lennernas, H., Membrane transport of drugs in different regions of the intestinal tract of the rat, J. Pharm. 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

The intestinal permeability (Peff) is a major determinant of fraction drug absorbed, and quantitatively represents the principal membrane transport coefficient of the... 

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