Intestine target tissues

A couple of theories have been proposed to explain how dietary Ca might possibly affect Se utilization. It has been suggested that Se availability may be directly influenced by intestinal interactions involving Ca or minerals linked to Ca utilization (e.g., phosphorus) (Lowry et al., 1985). Indirect effects on the capacity of a target tissue to respond to Se are also considered possible means by which bioavailability or retention might be influenced (Parizek, 1978). It has also been conjectured (Hill and Matrone, 1970 Howell and Hill, 1978) that elements with valence shell electronic structures most similar to Se (i.e., Se , Se, and Se " ") are most likely to act antagonistically. Based on this criterion, Ca does not fit the profile of a probable Se antagonist. 

Lubiprostone has used as a novel PG compound for an oral treatment of constipation with a unique action directed to the target tissue, although it has low systemic availability following oral administration. It activates a locally acting chloride channel, which is a normal constituent of the apical membrane of the human intestine, and enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentration in the serum. In fasted rats administered doses of 1, 10, or lOOpg/kg of the compound, dose-dependent increases in the concentration of chloride ions in the bowel were detected, indicating that the compound opens chloride channels and promotes chloride ion transport in vivo [45]. 

In higher plants, carotenoids are produced in green leaves. In animals, conversion of carotenoids to vitamin A occurs in the intestinal wall. Storage is in the liver also kidney in rat and cat. Target tissues are retina, skin, bone, liver, adrenals, germinal epithelium. Commercial Vitamin A supplements are obtained chemically by extraction of fish liver or synthetically from citral or /3-ionone. 

Factors which tend to decrease bioavailability of pyridoxine include (1) Administration of isoniazid (2) loss in cooking (estimated at 30-45%)—vitamin is water-soluble, (3) diuresis and gastrointestinal diseases (4) irradiation. Availability can be increased by stimulating intestinal bacterial production (very small amount), and storage in liver. The target tissues of Be are nervous tissue, liver, lymph nodes, and muscle tissue. Storage is by muscle phosphorylase (skeletal muscle—small amount). It is estimated that 57% of the vitamin ingested per day is excreted. The vitamin exerts only limited toxicity for humans. 

In the biosynthesis of vitamin D substances, precursors include cholesterol (skin + ultraviolet radiation) in animals ergosterol (algae, yeast + ultraviolet radiation), Intermediates in the biosynthesis include preergocaldferol, tachysterol, and 7-dehydrocholesterol. Provitamins in very small quantities are generated in the leaves, seeds, and shoots of plants. In animals, the production site is the skin. Target tissues in animals are bone, intestine, kidney, and liver. Storage sites in animals are liver and skin. 

Advances have been made in the localization of the cellular sites of l,25-(OH)2D3 in target tissue. Receptor proteins have been extracted, and, in the case of the chick intestinal receptor, purified to homogeneity.451 The ability of l,25-(OH)2D3 to stimulate absorption of calcium is blocked reversibly by inhibitors of RNA and protein synthesis. This suggests that l,25-(OH)2D3 functions by a nuclear mechanism. 

However, calcitriol is well established as the most potent agent with respect to stimulation of intestinal calcium and phosphate transport and bone resorption. Calcitriol appears to act on the intestine both by induction of new protein synthesis (eg, calcium-binding protein) and by modulation of calcium flux across the brush border and basolateral membranes by a means that does not require new protein synthesis. The molecular action of calcitriol on bone has received less attention. However, like PTH, calcitriol can induce RANK ligand in osteoblasts and proteins such as osteocalcin, which may regulate the mineralization process. The metabolites 25(OH)D and 24,25(OH)2D are far less potent stimulators of intestinal calcium and phosphate transport or bone resorption. However, 25(OH)D appears to be more potent than l,25(OH)2D in stimulating renal reabsorption of calcium and phosphate and may be the major metabolite regulating calcium flux and contractility in muscle. Specific receptors for l,25(OH)2D exist in target tissues. However, the role and even the existence of receptors for 25(OH)D and 24,25(OH)2D remain controversial. 

For nearly 30 years following the discovery of vitamin D3, relatively little was known about its metabolic fate in man. It was thought that vitamin D3 acted directly on the target tissues of intestine and bone. However, the time lag reported by Carlsson (97) between the... 

Chylomicrons are synthesized in the intestine and transport dietary triacylglycerols to skeletal muscle and adipose tissue, and dietary cholesterol to the liver. At these target tissues the triacylglycerols are hydrolyzed by lipoprotein lipase on the surface of the cells and the released fatty acids are taken up either for metabolism to generate energy or for storage. The resulting cholesterol-rich chylomicron remnants are transported in the blood to the liver where they are taken up by receptor-mediated endocytosis. 

Comparative Toxicokinetics. The toxicity of DEHP differs among species. This is due both to differences in pharmacokinetics and species-specific differences in target tissue susceptibilities. For example, there are species differences in the rate of hydrolysis of DEHP to MEHP in the intestine. Hydrolytic activity is highest in the mouse, followed by the rat, guinea pig and hamster (Albro 1986 ... 

In essence, first-pass elimination kinetics means that, if a chemical administered by any route is metabolized before it reaches a target tissue, it will cause no response in that tissue. Hence, the forms of P-450 induced in the intestine and liver metabolize most of the benzo [a] pyrene given orally to the Ah-responsive mouse the amount of parent drug or its metabolites reaching the bone marrow is therefore greatly decreased. 

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

Target tissue for 1,25-dihydroxycholecalciferol, among others, is the intestine, where a Ca2+-binding protein is synthesized under its influence. 

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