In intestine

N. Roland, L. Nugon-Baudon and S. Rabot, in Intestinal Flora, Immunity Nutrition and Health, ed. A. P. Siinopoulos, T. Con ing and A. Rerat, World Reviews of Nutrition and Dietetics, Karger, Basel, 1993, vol. 74, pp. 123-148. 

Raymond-Hamet has given much attention to the action of the Rauwolfia alkaloids. Using Siddiqui s ajrhalinine, he found that it provokes hypotension accompanied by renal dilatation and exerts a true sympathi-colytic action. 1 Ajmaline and serpentine also induce hypotension and a decrease in intestinal action serpentinine diminishes the renal constrictive action of adrenaline, but does not alter its hypertensive effects. ... 

A great many organic quaternary bases can inhibit the action of acetyl choline in organ systems activated by that neurotransmitter and thus possess anticholinergic-antispasmodic activity. One such agent is methantheline bromide (4), used in the treatment of peptic ulcer and as an antispasmodic agent in intestinal disorders. Its synthesis Involves Friedel-Crafts cyclization of o-... 

Chan LM, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21 25—51... 

Nausea is often assumed to be a low level stimulation of the vomiting reflex. However, vomiting occurs without nausea in intestinal obstruction and in space... 

Entamoeba histolytica is an anaerobic rhizopod that occurs in tropical and subtropical areas. It can cause intestinal and extraintestinal manifestations. It is transmitted orally by ingestion of cysts that develop into trophozoites in the large intestine. Amebic trophozoites release several cytolytic factors, e.g. amoe-bapore, which enable the parasite to invade tissue. In intestinal amoebiasis, E. histolyticatrophozoites invade the intestinal mucosa, causing a form of ulcerative colitis with bloody and mucous diarrhoea. Extraintestinal manifestation of amebiasis results in abscess formation, usually in the liver but sometimes in the brain. 

Tissue-Specific Expression. In the adult rodent, PPARy is expressed in brown and white adipose tissue, and at lower levels in intestine, retina, skeletal muscle, and lymphoid organs. In human, PPARy is most abundantly expressed in white adipose tissue and at lower levels in skeletal muscle, the heart, and liver, but not in lymphoid tissues, although PPARy has been identified in macrophages in human atheromas. 

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

Because the oral aminoglycosides are poorly absorbed, they are useful to suppressing gastrointestinal bacteria The oral aminoglycosides kanamycin (Kantrex) and neomycin (Mycifradin) are used preoperatively to reduce the number of bacteria normally present in the intestine (bowel prep). A reduction in intestinal bacteria is thought to lessen the possibility of abdominal infection that may occur after surgery on the bowel. 

Constipation, caused by a decrease in intestinal motility, may occur in tiiose taking one of tiiese drag s on a regular basis. Drowsiness may occur widi die use of diese dm, but at times tins adverse reaction is desirable Fbr example when atropine is used preoperatively to reduce die production of secretions in die respiratory tract, drowsiness is part of die desired response... 

Figure 3. Section of intestine from fetus whose mother was dosed orally with 1 fj g/kg/day of 2,3,7,8-tetrachlorodihenzo-p-dioxin during gestation days 6-15 (Note hemorrhage in intestinal lumen) (lOOX)...

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

To correctly predict overall oral absorption, drug metabolism in intestinal epithelial cells by cytochrome P450 enzymes should also be considered. The prediction of drug metabolism has already been covered in detail in Chapter 18. 

The transceUular movement of sugars involves one additional component a uniport that allows the glucose accumulated within the cell to move across a different surface toward a new equihbrium this occurs in intestinal and renal cells, for example. 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

Palytoxin (PTX) is one of the most potent marine toxins known and the lethal dose (LD q) of the toxin in mice is 0.5 Mg/kg when injected i.v. The molecular structure of the toxin has been determined fully (1,2). PTX causes contractions in smooth muscle (i) and has a positive inotropic action in cardiac muscle (4-6). PTX also induces membrane depolarization in intestinal smooth (i), skeletal (4), and heart muscles (5-7), myelinated fibers (8), spinal cord (9), and squid axons (10). PTX has been demonstrated to cause NE release from adrenergic neurons (11,12). Biochemical studies have indicated that PTX causes a release of K from erythrocytes, which is followed by hemolysis (13-15). The PTX-induced release of K from erythrocytes is depress by ouabain and that the binding of ouabain to the membrane fragments is inhibited by PTX (15). 

In intestinal cells, carotenoids can be incorporated into CMs as intact molecules or metabolized into mainly retinol (or vitamin A), but also in retinoic acid and apoc-arotenals (see below for carotenoid cleavage reactions). These polar metabolites are directly secreted into the blood stream via the portal vein (Figure 3.2.2). Within intestinal cells, retinol can be also esterified into retinyl esters. 

In intestinal contents and faeces from germfree rats quite high amounts of galacturonan were found, especially in the case of the pectin with the highest DE (Table 3). The isolated pectins were depolymerized to a small extent. The molecular weight distribution of pectins from intestinal contents and faeces remained relatively unchanged (Figures 1 and 2). 

Pectin in intestinal contents and in faeces of conventional rats... 

This gene is broadly distributed in skeletal muscle, heart, uterus, and in a variety of non-muscle cells. The mRNA levels are particularly high in intestine, lung and spleen, whereas they are very low in liver, testes, kidney and pancreas. In the muscle tissue SERCA3 may be confined primarily to non-muscle cells (vascular smooth muscle, endothelial cells, etc.). The C-terminus of SERCA3 is Asp-Gly-Lys Lys-Asp-Leu-Lys (Table I) it may serve as a sorting signal for retention of the enzyme in the endoplasmic reticulum [57]. 

Recently, Tse et al. [73] and Orlowski et al. [74] have cloned a third isoform of Na /H exchanger (named NHE-3). The inferred 832-amino acid sequence of rabbit NHE-3 is 41% identical with NHE-1, 44% identical with NHE-2, and has a similar secondary structure. In contrast to NHE-1 and NHE-2, NHE-3 is only expressed in epithelia in intestine and kidney. Moreover, administration of glucocorticoids, which stimulates transport activity of the apical Na /H" exchanger in rabbit intestine, increased levels of NHE-3 transcripts but did not affect NHE-1 or NHE-2 [75]. Taken together, these results suggest that NHE-3 may encode a resistant-type Na /H exchanger of epithelia. A fourth Na /H exchanger isoform (NHE-4) is preferentially expressed in stomach [74]. 

Like other xenobiotics, cannabinoids also undergo extensive metabolism in the human body to increase their hydrophihc properties for a facihtated ehmination. The metaboHsm of A9-THC has been very well investigated. More than 100 metabolites of A9-THC are known [99] and a good overview of the most important human metaboHtes is given in [100]. MetaboHsm takes place mainly in hepatic microsomes, but also in intestines, brain. 

Grisham, M.B., Hernandez, L.A. and Granger, D.N. (1986). Xanthine oxidase and neutrophil infiltration in intestinal ischaemia. Am. J. Physiol. 251, G567-G574. 

Van der Vliet, A. and Bast, A. (1992). Role of reactive oxygen species in intestinal diseases. Free Rad. Biol. Med. 12, 499-513. 

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