Binding in tissues

Helander KG. Kinetic studies of formaldehyde binding in tissue. Biotech. Histochem. 1994 69 177-179. 

Schwab BW, Hand H, Costa LG, et al. 1981. Reduced muscarinic receptor binding in tissues of rats tolerant to the insecticide disulfoton. Neurotoxicology 2 635-647. 

The polymyxins are slowly excreted by glomerular filtration the slow elimination rate is due to binding in tissues. Elimination is decreased in patients with renal disease, and drug accumulation can lead to toxicity. Sodium coUstimethate, the parenteral preparation, binds less to tissue and is excreted faster than the free base. 

Bylund DB, Ray-Prenger C, Murphy TJ. a2A and a2B adrenergic receptor subtypes antagonist binding in tissues and cell lines containing only one subtype. J Pharmacol Exp Ther 1988 245 600-607. 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

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 enzymatic activity of these potentially harmful enzymes is tightly controlled. Once transcribed into protein, MMPs are expressed as inactive zymogens and require distinct activation processes to convert them into active enzymes. After secretion, MMP-activity is regulated by the noncovalent binding of tissue inhibitors of metalloproteinases ( TIMPs) as shown in Fig. 2 for MMP-2 and TIMP-2. Four TIMPs have been identified so far TIMP-1, TIMP-2, TIMP-3, and TIMP-4. All known MMPs can be inhibited by at least one of the four known TIMPs. Nevertheless, individual differences with regard to bond strength and thus the magnitude of inhibition of a particular MMP do exist. 

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

Differences in the equilibrium dissociation constant, K, for the binding of the various saxitoxins to the sodium channel binding site largely determine the differences in the potencies of the toxins in whole animal assays and in tissue preparations. 

Monoamine concentrations or receptor binding in brain tissue post-mortem. 

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