Transporters tissue distribution

Because thyroid hormones are protein boun i throughout the general circulation as well as in the cell membranes and nucleus, protein binding is central to the transport, tissue distribution and metabolism rates of the various thyroid analogues (29). Current theory proposes that the hormone first binds at a specific site on the protein receptor and then an interaction... 

Transporter Tissue Distribution Localization Substrates Inhibitors ... 

The tissue distribution of substrates of transporters involved in the active transport into or out of tissues... 

Several studies of tissue distribution in humans after inhalation exposure to trichloroethylene report levels in the blood (Astrand and Ovrum 1976 Monster et al. 1976 Muller et al. 1974). Once in the bloodstream, trichloroethylene may be transported rapidly to various tissues where it will likely be metabolized. Trichloroethylene was detected in the blood of babies at birth after the mothers had received trichloroethylene anesthesia (Laham 1970), and detectable levels (concentrations not reported) have been found in the breast milk of mothers living in urban areas (Pellizzari et al. 1982). Post-mortem analyses of human tissue from persons with unspecified exposure revealed detectable levels of trichloroethylene (<1-32 pg/kg wet tissue) in most organs (McConnell et al. 1975). The relative proportions varied among individuals, but the major sites of distribution appeared to be body fat and the liver. 

In this chapter we will review the recent investigations of the structure of both the a and P subunit, and the function of gastric H,K-ATPase. We will proceed from a brief overview of the tissue distribution to a successive discussion of structure, kinetics, transport properties, lipid dependency, solubilization and reconstitution, and inhibitors of H,K-ATPase that may label functionally important domains of the enzyme. 

FIGURE 24.3 Distribution of CBP. (a) Analysis of tissue distribution by Western blotting, (b) Immunohistochemistry of the midgut epithelium. CBP was not detected in the goblet cells (G) of the midgut epithelium, which are thought to be involved in ion transport. 

Saito, H., et al. Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim. Biophys. Acta 1996, 1280, 173-177. 

Wu, X., et al. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 2000, 1466, 315-327. 

Fukumoto, H., et al. Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein. Proc. Natl. Acad. Sci. U. S. A. 1988, 85, 5434-5438. 

Current information indicates that OATP-E [30] is ubiquitously expressed in tissues [30, 37]. Some substrates transported by OATP-E include estrone-sulfate [30], prostaglandin E2 [30] and taurocholate [37]. The capacity for T3 and T4 transport and the wide tissue distribution suggests that OATP-E is largely responsible for the peripheral uptake of thyroid hormone [37]. Further studies are required to assess whether OATP-E is an important determinant of drag distribution. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Uptake is the process by which chemicals (either dissolved in water or sorbed onto sediment and/or suspended solids) are transferred into and onto an organism. For surfactants, this generally occurs in a series of steps a rapid initial step controlled by sorption, where the surface phenomenon is especially relevant then a diffusion step, when the chemical crosses biological barriers, and later steps when it is transported and distributed among the tissues and organs. 

Shitara, Y., Horie, T. and Sugiyama, Y. (2006) Transporters as a determinant of drug clearance and tissue distribution. European Journal of Pharmaceutical Sciences, 27, 425-446. 

The specific mechanism by which chlordecone is transferred from the gut, lungs, or skin to the blood is not known. However, the preferential distribution of chlordecone to the liver rather than the fat tissues suggests that it may be transported in the plasma differently from other organochlorine compounds (Soine et al. 1982). In vitro and in vivo studies of human, rat, and pig plasma showed that chlordecone is preferentially bound by albumin and high-density lipoproteins (HDL), which may explain its tissue distribution. Other organochlorine pesticides such as aldrin and dieldrin bind to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) and distribute preferentially to fat (Soine et al. 1982). 

Some specific molecules that are important in protein-drug interactions have been studied extensively, including cytochrome P450 (CYP450), receptors, membrane transporters, and antibodies (see Table 1.6). Databases about these molecules may also contain information about SNP effects, tissue distribution, and interacting substrates. 

Before glycolysis from glucose can begin, glucose has to be transported into the ceU. This is achieved by a transporter protein, in the plasma membrane (Chapter 5). There are five different types of glucose transporter, all encoded by separate genes. The proteins have slightly different properties, different tissue distribution and somewhat different roles in these tissues. Their roles are briefly described in Table 6.1. A sixth transporter is specific for fructose it is... 

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