Transporters gastrointestinal tract

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

A new interpretation of salicylic acid transport across the lipid bilayer implications of pH-dependent but not carrier-mediated absorption from the gastrointestinal tract. /. Pharmacol. 

Jackson. M. J., Drug transport across gastrointestinal epithelia, in Johnson, L. R. (ed.), Physiology of the Gastrointestinal Tract, 2nd ed., Raven Press, New York, 1987, pp. 1597-1621. 

Biological Transport Phenomena in the Gastrointestinal Tract Cellular Mechanisms... 

In the example above, the solutions are assumed to be well stirred and mixed the aqueous resistance is negligible, and the membrane is the only transport barrier. However, in any real case, the solutions on both sides of the membrane become less and less stirred as they approach the surface of the membrane. The aqueous diffusion resistance, therefore, very often needs to be considered. For example, for very highly permeable drugs, the resistance to absorption from the gastrointestinal tract is mainly aqueous diffusion. In the section, we give a general solution to steady diffusion across a membrane with aqueous diffusion resistance [5],... 

S Suzuki, WI Higuchi, NFH Ho. Theoretical model studies of drug absorption and transport in the gastrointestinal tract. I. J Pharm Sci 59 644-651, 1970. 

Gastrointestinal absorption of lead is influenced by dietary and nutritional calcium and iron status. An inverse relationship has been observed between dietary calcium intake and PbB concentration (Mahaffey et al. 1986 Ziegler et al. 1978). Complexation with calcium (and phosphate) in the gastrointestinal tract and competition for a common transport protein have been proposed as possible mechanisms for this interaction (Barton et al. 1978a Heard and Chamberlain 1982). Absorption of lead from the... 

All of the organ systems in the body, except the reproductive system, contribute to the maintenance of homeostasis (see Table 1.1). For example, the gastrointestinal tract digests foods to provide nutrients to the body. The respiratory system obtains oxygen and eliminates carbon dioxide. The circulatory system transports all of these materials and others from one part of the body to another. The renal system eliminates wastes and plays a role in regulating blood volume and blood pressure. 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

The circulatory system carries out many important functions that contribute to homeostasis. It obtains oxygen from the lungs nutrients from the gastrointestinal tract and hormones from the endocrine glands and it delivers these substances to the tissues that need them. Furthermore, it removes metabolic waste products, such as carbon dioxide, lactic acid, and urea, from the tissues. Finally, it contributes to the actions of the immune system by transporting antibodies and leukocytes to areas of infection. Overall, the circulatory system plays a vital role in maintenance of optimal conditions for cell and tissue function. 

In the enterocyte as it enters the absorptive zone near to the villus tips, dietary iron is absorbed either directly as Fe(II) after reduction in the gastrointestinal tract by reductants like ascorbate, or after reduction of Fe(III) by the apical membrane ferrireductase Dcytb, via the divalent transporter Nramp2 (DCT1). Alternatively, haem is taken up at the apical surface, perhaps via a receptor, and is degraded by haem oxygenase to release Fe(II) into the same intracellular pool. The setting of IRPs (which are assumed to act as iron biosensors) determines the amount of iron that is retained within the enterocyte as ferritin, and that which is transferred to the circulation. This latter process is presumed to involve IREG 1 (ferroportin) and the GPI-linked hephaestin at the basolateral membrane with incorporation of iron into apotransferrin. (b) A representation of iron absorption in HFE-related haemochromatosis. 

Herrera-Ruiz, D., et al. Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues. AAPS PharmSci. 2001, 3, E9. 

Because the amounts and density of these transporters vary along the gastrointestinal tract, it is necessary to introduce a correction factor for the varying transport rates in the different luminal and enterocyte compartments. Due to the lack of experimental data for the regional distribution, and Michaelis-Menten constants for each drug in Table 18.2, we fitted an intrinsic (concentration-independent) transport rate for each drug to closely approximate the experimental %HIA. This... 

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