Receptors in different tissues

James Black, who was one of the most important contributors in the development of the /6-blockers, applied the lesson learnt there for the development of the most successful drug of the 1980s. He and others interpreted the observation that alkyl-substituted histamine analogs did not exhibit equal activity on histamine receptors in different tissues as a result of the existence of more than one histamine receptor. Indeed, it could be... 

Pillai SP, Lee CW (2010) Species and age related differences in the type and distribution of influenza virus receptors in different tissues of chickens, ducks and turkeys. Virol J 7 5... 

The nicotinic receptor is a channel-type receptor composed of four non-identical subtmits which open an ion gate upon activation, allowing the build-up of a membrane potential which in turn uansmits the signal further down the nerve or muscle. The stmcture of the receptors will be discussed in more detail later. The effects resulting from the activation of the muscarinic and nicotinic receptors in different tissues are summarised in Table 16.1. 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

There are also specific differences in the location of receptors in various tissues and in various animals. If mice and rats are sufficiently stable to effects of histamine, then guinea pigs and humans will be very sensitive. 

BENEFICIAL AND TOXIC EFFECTS MEDIATED BY IDENTICAL RECEPTORS BUT IN DIFFERENT TISSUES OR BY DIFFERENT EFFECTOR PATHWAYS... 

Many drugs produce both their desired effects and adverse effects by acting on a single receptor type in different tissues. 

A model of thyroid hormone action is depicted in Figure 38-4, which shows the free forms of thyroid hormones, T4 and T3, dissociated from thyroid-binding proteins, entering the cell by active transport. Within the cell, T4 is converted to T3 by 5 -deiodinase, and the T3 enters the nucleus, where T3 binds to a specific T3 receptor protein, a member of the c-erb oncogene family. (This family also includes the steroid hormone receptors and receptors for vitamins A and D.) The T3 receptor exists in two forms, a and B. Differing concentrations of receptor forms in different tissues may account for variations in T3 effect on different tissues. 

In a very thoughtful investigation of solvent systems to model membrane characteristics, Leahy et al. (1989, 1992) have argued that two receptors sited in different tissues (or membranes) could exist in environments that are very different in hydrogen bonding character one may be surrounded by amphiprotic groups (as in a protein) or by proton donors the other may be surrounded by proton acceptors (as in a phospholipid membrane). 

Cell specificity of mineralocorticoid action is achieved in a different manner. Aldosterone, cortisol, and corticosterone bind with similar affinities to mineralocorticoid and glucocorticoid receptors. However, aldosterone activates only its own receptor in target tissues such as the kidney because of an enzyme, 110-hydroxysteroid dehydrogenase, that converts the prevalent glucocorticoids into inactive 11-keto derivatives but does not affect aldosterone. 

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