Gastrointestinal tract binding sites

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. 

Two membrane-receptive binding sites called and receptors mediate the pharmacological effect of histamine. Hj receptors are located in smooth muscle of vessels, and bronchial and gastrointestinal tract, while H2 receptors are found in the walls of the stomach, myocardium, and certain vessels. 

After oral administration, sulfonamides are rapidly and completely absorbed from gastrointestinal tract and approximately 70 to 90 percent of oral dose reaches to the blood stream, but the binding with plasma proteins differ considerably among different groups. The highly plasma protein bound sulfonamides have longer action. The main site of absorption is small intestine. 

Absorption of a mycotoxin will occur when it crosses body membranes and enters the blood stream. The primary sites of mycotoxin absorption are the gastrointestinal tract (ingestion of contaminated food), lungs (inhalation of contaminated particles or toxin-containing fungal spores) and the skin (direct contact with contaminated materials or pure mycotoxins). When the mycotoxin enters the blood it is then available for distribution. Livers and kidneys have a high capacity to bind many mycotoxins while other mycotoxins are highly lipophilic and can concentrate in body fat. In the final outcome a toxic response by a mycotoxin will be critically influenced by the rate of absorption, distribution, biotransformation and excretion (Smith et al., 1994). 

The key enzymes of the system are the cytochrome P-450 enzymes, which have active sites that contain an iron atom that cycles between the +2 and +3 oxidation states. These enzymes bind to the substrate and molecular 02as part of the substrate oxidation process. Cytochrome P-450 is found most abundantly in the livers of vertebrates, reflecting the liver s role as the body s primary defender against systemic poisons. Cytochrome P-450 occurs in many other parts of the body, such as the kidney, ovaries, testes, and blood. The presence of this enzyme in the lungs, skin, and gastrointestinal tract may reflect their defensive roles against toxicants. 

Eosinophils are leukocytes that contain characteristic cationic proteins in their granules that bind the acidic dye eosin. In contrast to neutrophils, eosinophils are minority cells in the blood and are predominantly tissue-dwelling cells found at sites in contact with the environment the mucosal surfaces of the lung, gastrointestinal tract, and genitourinary tract. Selective accumulation of eosinophils, as opposed to neutrophils, is one of the major pathological features of the inflammatory response to infection with parasitic helminths, and in several diseases such as asthma, allergic rhinitis, and atopic dermatitis. A key step in leukocyte recruitment is the local production of chemoattractant molecules that orchestrate the adhesive interactions between leukocytes and the vascular endothelium. 

Pharmacokinetics. Heparin is poorly absorbed from the gastrointestinal tract and is given i.v. or S.C. once in the blood its effect is immediate. Heparin binds to several plasma proteins and to sites on endothelial cells it is also taken up by cells of the reticuloendothelial system and some is cleared by the kidney. Due to these factors, elimination of heparin from the plasma appears to involve a combination of zero-order and first-order processes, the effect of which is that the plasma biological effect alters disproportionately with dose, being 60 min after 75 units per kg and 150 min after 400 units per kg. 

The glycoproteins (ricin) are poorly absorbed from the gastrointestinal tract however, once absorbed, they most likely follow a distribution pattern similar to that of albumin. Many cell surfaces contain receptors specific for the ricin molecules. This molecule consists of two subunits, A and B, bound by a disulfide link. When this link is broken, the B subunit binds to galactose-containing receptors in the cell wall and is transported intracellularly. The A subunit inhibits protein synthesis. The liver, spleen, adrenal cortex, and bone marrow are the primary sites of distribution. The biotransformation and elimination of toxalbumins are poorly understood. The elimination half-life in one patient was 2 days. The reported disappearance of ricin from the plasma is according to first-order kinetics when... 

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