Distribution, tissue

The tissue distribution and levels of RBP in normal and in retinol-deficient rats were measured in order to explore the role of different tissues in the metabolism of RBP (J. E. Smith et al., 1975). The tissues examined included liver, kidney, fat, muscle, brain, eye, salivary gland, thymus, lung, heart, intestine, spleen, adrenal, testes, thyroid, and red blood cells. The RBP levels were low or very low in tissues other than liver, kidney, and serum and varied from 12 p.g/g of tissue for normal spleen to an undectable level in red blood cells. Much of the RBP in the tissues with low levels was most likely due to residual serum in the samples. In general, except for liver, RBP levels were lower in tissues from retinol-deficient rats than in those fixim normal rats. In normal rats, the liver, kidney, and serum levels were 30 4 (mean SEM), 151 22, and 44 3 p.g/g, respectively. In retinol-deficient rats, the liver RBP level was about three times the normal level whereas the kidney and serum levels were about one-fifth the normal values. It was suggested that die levels of RBP in normal as compared to deficient liver, serum, and kidney appear to reflect the relative rates of RBP secretion and turnover (see later discussion). 

Brain Olfactory Intestinal Tract Steroidogenic Tissues 

Studies in rabbits, rats, mice, hamsters, and monkeys demonstrate that arsenic, administered orally or parenterally, as either As(III) or As(V), is rapidly distributed throughout the body. Many of these studies have used radiolabeled arsenic and it is noteworthy that arsenic-derived radioactivity is generally present in all examined tissues (Marafante, Bertolero and Edel, 1982 Kenyon, Del Razo and Hughes, 2005a Kenyon, Del Razo and Hughes, 2005b Lindgren, Vahter and Dencker, 1982 Vahter et al., 1982 Vahter and Marafante, 1985). 

Arsenic is capable of crossing the blood-brain barrier since it is found in brain tissue after oral or parenteral administration of inorganic As(V) or inorganic As(III) in all studied species. However, the levels are uniformly low both across time and relative to other tissues, which indicate that arsenic does not readily cross the blood-brain barrier or accumulate in brain tissue following acute dosing (Marafante, Bertolero and Edel, 1982 Yamauchi and Yamamura, 1985 Lindgren, Vahter and Dencker, 1982 Dang, Jaiswal and Somasundaram, 1983 Yamauchi and Yamamura, 1983 Vahter et al., 1982 Vahter and Marafante, 1985). 

The discussion and studies cited previously generally reflect overall tissue distribution of total arsenic after acute exposure in the case of laboratory animals or unknown exposures in the case of humans. Advances in analytical technology in the last decade have facilitated the identification of tissue-specific patterns of metabolite distribution and accumulation in laboratory animals. Kenyon, Del Razo and Hughes (2005a) found that inorganic arsenic was the predominant form of arsenic in the liver and kidney up to two hours post administration of 10 or 100 p mol As kg-1 as inorganic As(V) to female mice, whereas 

Concentrations of oligonucleotide in the liver and kidney of mice and monkeys after three months of treatment were dose-dependent, but were generally less than dose-proportional (especially in the case of mouse kidney), indicating a saturable process for tissue uptake and distribution. Tissue concentrations of oligonucleotides after four and 13 weeks of treatment were generally higher in monkeys than in mice at comparable dose levels [26]. In both mice and monkeys, it appeared that steady-state concentrations were almost attained in liver and kidney 

Sequence Half-life (days) Cone. (ng/g)a) at Steady-state  

While distribution to tissues relies on the mechanism of plasma clearance, whole-body clearance is the result of metabolism and the excretion of low molecular-weight oligonucleotides. Ubiquitous nucleases are known to metabolize oligonu- 

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BK actions are mediated through at least two types of GPCR B and B2. At the B receptor, des-Arg BK is more potent than BK. The converse is tme at the B2 receptor. The effects of BK are primarily mediated by activation of the B2 receptor because the B receptor has limited tissue distribution and is iaduced by noxious stimuli such as apamin or an inflammatory mediator-type response. The existence of a B receptor was suggested on the basis of limited efficacy of known antagonists ia some systems. A B receptor may also exist. The human B2 receptor has been cloned. 

Initially, it was beheved that the abiUty of xanthines phosphodiesterase (PDF) led to bronchodilation (Fig. 2). One significant flaw in this proposal is that the concentration of theophylline needed to significantly inhibit PDE in vitro is higher than the therapeutically useful semm values (72). It is possible that concentration of theophylline in airways smooth muscle occurs, but there is no support for this idea from tissue distribution studies. Furthermore, other potent PDE inhibitors such as dipyridamole [58-32-2] are not bronchodilators (73). EinaHy, although clinical studies have shown that neither po nor continuous iv theophylline has a direct effect on circulating cycHc AMP levels (74,75), one study has shown that iv theophylline significant potentiates the increase in cycHc AMP levels induced by isoproterenol (74). 

Florfenicol has a wide tissue distribution, similar to that reported for chloramphenicol in calves and thiamphenicol in humans (43,44). Chloramphenicol attains concentrations higher than the corresponding plasma concentrations in bile and urine, as does florfenicol (43). Unlike florfenicol, chloramphenicol concentrations in the Hver, kidney, spleen, and lungs are less than corresponding plasma concentrations. However, chloramphenicol penetrates the brain and CSF much better than does florfenicol, reaching values equal to plasma concentrations in the brain. The distribution of thiamphenicol into the kidney, urine, and muscles of humans compared with corresponding plasma concentration is similar to what was observed for florfenicol in calves (44). The penetration of thiamphenicol into the CSF is much smaller than that of florfenicol in calves. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

AdCy Effect of Gaj Effect of gpy Effects of Ca2+and/or calmodulin Effects of protein kinases Tissue distribution Physiological functions... 

ChEs present several amphiphilic and soluble homo-and hetero-oligomeric molecular forms in tissues and body fluids, with different tissue distributions (Fig. 1). 

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

The endothelin receptor subtypes show differences in their signal transduction, ligand binding and tissue distribution. The ETA receptor is isopeptide-selective and binds ET-1 and ET-2 with the same and ET-3 with 70-100-fold lower affinity. The ETB receptor binds all three isoforms with the same affinity. 

The insulin-binding domain of the INSR is located within a cystein-rich region of the a-subunits. Alternative splicing of exon 11 generates two isoforms of the a-subunit which differ in their C-terminus and in their tissue distribution (type A leukocytes type B liver type A and B skeletal muscle and fat). The isoforms differ in their affinity to insulin (A > B), but then-relevance for normal and impaired insulin action is not entirely clear [1,2]. 

Receptor Endogenous ligands Main tissue distribution Signalling Main biological effects... 

Like all neuropeptides, NT is synthesized as part of a larger precursor that also contains neuromedin N (NN), a 6 amino acid neurotensin-like peptide (Table 1). Pro-NT/NN is processed in the regulated secretory pathway of neuroendocrine cells by prohormone convertases PCI, PC2 and PC5-A that belong to a larger family of proprotein convertases. Due to differential cleavage specificity and tissue distribution of the convertases, pro-NT/NN processing gives rise to approximately a 1 1 and a 5 1 ratio of NT over NN content in the brain and gut, respectively. The peptides are stored in secretory vesicles and released from neuroendocrine cells in a Ca2+-dependent manner. NT and NN actions are terminated by desensitization of the... 

Satake H, Kawada T (2006) Overview of the primary structure, tissue distribution, and function of tachykinins and their receptors. Curr Drug Targets 7 963-974... 

Due to their physicochemical properties trace amines can pass the cell membrane to a limited extent by passive diffusion, with the more lipophilic PEA and TRP crossing membranes more readily than the more polar amines TYR. and OCT. In spite of these features, trace amines show a heterogeneous tissue distribution in the vertebrate brain, and for TYR. and OCT storage in synaptic vesicles as well as activity-dependent release have been demonstrated. So far, trace amines have always been found co-localized with monoamine neurotransmitters, and there is no evidence for neurons or synapses exclusively containing trace amines. 

With respect to tissue distribution, the available data is limited to mRNA transcripts which, for all TAARs studied so far, are present at generally low levels when compared to e.g., 5-HT and DA receptors. The most... 

S3B Pharmacokinetics Guidance for Repeated Dose Tissue Distribution Studies Toxicity Testing... 

Wagner, M.C., Barylko, B., Albanesi, J.P. (1992). Tissue distribution and subcellular localization of mammalian myosin I. J. Cell Biol. 119, 163-170. 

Penninks AH, Hilgers L, Seinen W (1987) The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats. Toxicology, 44 107-120. 

There is limited information available regarding the distribution of methyl parathion after dermal exposure in humans. Two subjects, dermally exposed to methyl parathion, had 2.74 and 1.23 mg on their hands. Twenty-four hours after exposure, the serum levels were 0.027 and 0.032 mg/L, respectively (Ware et al. 1973). Twelve hours after cotton fields were sprayed, five men entered the treated fields for 5 hours. An average of 1.7 mg methyl parathion was detected on their hands. Serum concentrations averaged 0.156 mg/L in these subjects after 3 hours of exposure. Levels decreased to 0.1 and 0.002 mg/L at 2 and 24 hours postexposure, respectively (Ware et al. 1975). Although 0.5 mg methyl parathion was detected on the hands of four subjects, none was found in the serum (Ware et al. 1974). No information on the tissue distribution of methyl parathion in humans was found. 

Kuriyama, S.N., Wanner, A., and Fidalgo-Neto, A.A. (2007). Developmental exposnre to low-dose PBDE-99 Tissue distribution and thyroid hormone levels. Toxicology 242, 80-90. 

McMahon B.M., Mays D., Lipsky J., Stewart J.A., Fauq A., Richelson E. Pharmacokinetics and tissue distribution of a peptide nucleic acid after intravenous administration. Antisense Nucleic Acid Drug Dev. 2002 12 65-70... 

Table III. Tissue Distribution in Dams Following a Single Oral Dose of 200 /Ag/kg of C -2,3,7,8-Tetrachlorodibenzo- >-Dioxin on Gestation Day 16, 17, or 18 (/ g/gram of tissue)...

There is no available information on the absorption, excretion, or tissue distribution of TCDD in animals. Therefore, this study was done... 

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