Receptors chemical binding

British researchers Thomas Elliot (1877-1961) and John Langley (1852-1925) develop the idea of a receptor—a molecule to which chemicals bind and exert effects on a cell. 

NPs provide highly efficient catalysts and sensors due to their unique chemical and physical properties. NPs can be used as exo-active surfaces where a multitude of molecular receptors can bind analytes and generate a signal. Alternatively, NPs can be used as core-based materials in which biocatalytic processes can activate their core or they provide a biologically inert electrochemical label. As catalysts, NPs utilize their large surface area to volume ratio and enhance either electrochemical reactions or electron transfer at an electrode. The use of NPs in catalysts and sensors will continue as these functional materials serve as active units within these applications. 

The most popular OTC sleep aids are those that contain antihistamines such as diphenhydramine or doxylamine (Table 3.1). As noted in Chapter 1, nerve cells in the brain communicate with each other by secreting chemicals called neurotransmitters. One such neurotransmitter that regulates sleep is histamine. When histamine is released by a nerve cell, it diffuses over to the target nerve cell and binds to specialized proteins called receptors located on the outer surface of the nerve cell. These receptors are specially designed to bind only histamine, and when they do, the target nerve cell will become either activated or deactivated. In the brain, histamine serves the function of keeping us awake, and when drugs such as antihistamines are taken, they block the ability of histamine receptors to bind histamine. 

Figure 5.34 Mechanism of induction of CYP2B6 by a chemical such as the drug phenobarbital. This drug activates a nuclear receptor (CAR).This combines with the retinoid X receptor and binds to PBREM, as specific section of the CYP gene, which stimulates the production of CYP2B6 mRNA leading to the production of CYP2B6 protein and enzyme. Abbreviations CAR, constitutive androstane receptor RXR retinoid X receptor PBREM, phenobarbital-responsive enhancer module.

Experimental studies in laboratory rodents have demonstrated that a diverse array of chemical exposures suppress immune function (Table 19.2). In addition a limited number of clinical and epidemiologic studies have reported suppression of immune function and/or increased frequency of infectious and/or neoplastic disease following exposure of humans to some of these agents. From the description above it is clear there are a number of cellular and molecular targets for chemicals that act as immunosuppressants. Clearly, a chemical that disrupts cell proliferation would affect clonal expansion. Disruption of T cell maturation in the thymus is another potential mechanism for immune suppression. Chemicals may also interfere with receptor ligand binding at the cell... 

Kinetic toxicology, also known as metabolic or pharmacologic toxicology, involves toxicants that are transported and metabolized in the body. Such substances are called systemic poisons and they are studied under the discipline of systemic toxicology. Systemic poisons may cross cell membranes (see Chapter 3) and act on receptors such as cell membranes, bodies in the cells, and specific enzyme systems. The effect is dose responsive, and it is terminated by processes that may include metabolic conversion of the toxicant to a metabolic product, chemical binding, storage, and excretion from the organism. 

Tong, W., Lowis, D.R., Perkins, R., Chen, Y., Welsh, W.J., Goddette, D.W., Heritage, T.W., and Sheehan, D.M., Evaluation of quantitative structure-activity relationship methods for large-scale prediction of chemicals binding to the estrogen receptor, J. Chem. Inf. Comput. Sci., 38, 669-677, 1998. 

If most drugs achieve their effects via interaction with a receptor, then by what chemical binding force is this achieved Ehrlich recognized very early that the combining forces must be very loose. He wrote in 1900 If alkaloids, aromatic amines, antipyretics or aniline dyes be introduced into the animal body, it is a very easy matter, by means of water, alcohol or acetone, to remove all of these substances quickly and easily from the tissues. This is the reason why isolated organ tissue... 

The decrease in enzyme sorption by the chemically modified membrane implies that under these experimental conditions, the lysyl E-amino groups function as principle receptor or binding sites for enzyme protein (at least for E. coli g-galactosidase) and that the complexation mechanism involves interaction of the lysyl residues of collagen with enzyme amino acid chains as an initial step in the formation of a stable network of physicochemical bonds. 

---