Reversibility, and other aspects of receptors

Ehrlich was the first to note that other, more easily reversible, bonds were concerned in the action of most drugs. He wrote Tf 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 these substances quickly and easily from the tissues (Ehrlich, 1900). 

Between each reading, the tissue was washed with saline, which restored it to its original condition. (Result of assay 0.1 ml of unknown has the potency of 0.09 ml of standard.) (Gaddum, 1936.) 

These steroid—receptor complexes are formed in, or diffuse into, the nucleus where they bind to the chromatin (no steroid is bound in the absence of its protein). In this way, a length of DNA (codon) is de-repressed and produces the required mRNA which, in turn, uses cytoplasmic ribosomes to make the characteristic protein. So rapid is this process that the physiological response characteristic of the hormone can sometimes be seen within an hour. These are very typical examples of the induction of a characteristic protein (for a review of induction, see Cohen, 1966). 

Many other examples were then discovered. The principal androgenic steroid, dihydrotestosterone, was found to be quite specifically bound by an acidic protein in androgen-dependent tissues such as the prostate gland (Anderson and Liao, 1968). Corticosteroids, too, are bound by specific protein in the cytoplasm of liver and some other cells, and the complex enters the nucleus where it is bound by DNA. This leads to the appearance of a specific mRNA (its formation suppressable by actinomycin D) which, in turn, produces enzymes characteristic of the corticosteroid (Sekeris, 1971). A similar sequence governs the diuretic effect of aldosterone (Edelman, Bogoroch and Porter, 1963). 

8-Tetrachlorodibenzo-j -dioxin (2.28a), the much-discussed contaminant of trichlorophenol, is taken up by a receptor protein in the cytosol of liver, then transported to the nucleus where it induces cytochrome P-450 and aryl hydrocarbon hydroxylase. These seem to be beneficial properties, but in some strains of mice it induces expression of other genes which effects cellular involution, division, and differentiation, presumably using a normal cell- 

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