Receptor-effector complex

The fitting of space structures of a signal ceiirier and of a bioreceptor is, as it seems, a decisive factor of a sensory signal occurrence. On the other hand, the formation of unstable effector-receptor complexes is stabilised by non-valency effects. In this way, it is possible to explain a similarity of the character of odour between (-)-a-phellandrene and (-)-limonene [56]. 

The action of a hormone is defined as the primary effect on a cell, usually the binding of the hormone to a specific receptor and the resultant interaction between the hormone-receptor complex and an effector system within the cell. The effect of a hormone is an experimental observation that is made either in vitro or in vivo it can be molecular, biochemical or physiological but, when a sufficient number of effects are established, a relationship between the action and effects can be drawn. This can best be described as a pyramid (Figure 12.2). The. function of a hormone is an... 

Figure 12.8 Effector mechanism activation of a specific gene by hormone-receptor complex binding to DNA. A steroid is used to illustrate the mechanism. The hormone enters the cell and binds to its receptor (R) in the cytosol, the hormone-receptor complex enters the nucleus and binds to a specific sequence in the DNA that stimulates transcription of a gene or genes the resultant increase in mRNA increases the synthesis of specific proteins. The binding site on the DNA is specific and is usually termed a response element. Thyroxine (i.e. triiodothyronine) also uses this effector mechanism. Activation of genes, RNA processing to produce mRNA and translation are described in Chapter 20 (see Figures 20.20, 20.21 and 20.22).

These principles are similar to those that govern the relationship between an enzyme and its catalytic activity. For the hormone, R is equivalent to the enzyme, H to the substrate, and hormone-receptor complex to the enzyme-substrate complex. The activity of the substrate effector system is similar to the transition state. The cellnlar response to the hormone is similar to the catalytic role of the enzyme in the cell (Chapter 3),... 

Figure 14-1. Signaling via G protein-coupled receptors. Ligand binding to its cell-surface receptor initiates interaction of the receptor with the heterotrimeric G protein for which it is specific. A conformational change in the G protein brought about by binding of the ligand-receptor complex promotes exchange of GDP for GTP. The activated Gd-GTP dissociates from the Gp complex and both can interact with effectors, which carry on the signal to the mechanism that implements the cellular response.

The interactions between transmitters and their receptors are readily reversible, and the number of transmitter-receptor complexes formed is a direct function of the amount of transmitter in the biophase. The length of time that intact molecules of acetylcholine remain in the biophase is short because acetylcholinesterase, an enzyme that rapidly hydrolyzes acetylcholine, is highly concentrated on the outer surfaces of both the prejunctional (neuronal) and postjunctional (effector cell) membranes. A rapid hydrolysis of acetylcholine by the enzyme results in a lowering of the concentration of free transmitter and a rapid dissociation of the transmitter from its receptors little or no acetylcholine escapes into the circulation. Any acetylcholine that does reach the circulation is immediately inactivated by plasma esterases. 

An initial amplification often occurs at the level of the hormone-receptor complex. An activated receptor is capable of activating many downstream effector proteins. 

D + R- drug-receptor complex- effector molecule- effect... 

One component of the IL-12 receptor complex shows it to be related to gpl30. To date, a large number of receptors for IL-12 have been found but only on PBMC following activation with PHA or IL-2. Studies have found that the expression of IL-12R on a human y5 T-ceU line responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin. ... 

Signal pathways commonly amplify the initial signal received by the receptor during the course of the signal transduction (Fig. 3.10). In many cases only a few molecules of a hormone are sufficient to initiate an enzymatic reaction in a cell, in which many substrate molecules are turned over. The extent of amplification, or amplification factor, varies greatly at the different levels of the signal transmission. An initial amplification often occurs at the level of the hormone-receptor complex. An activated receptor is capable of activating many downstream effector proteins. 

Fig. 11.4 Schematic diagram ofthe 11-2 receptor complex. The II-2R is composed of three subunits, IL-2Ra, IL-2R/7 yc. The Box 1 and Box 2 domains are conserved among members ofthe cytokine receptor superfamily, and a variable spacer region V intervenes Boxl and Box2. The Boxl-V-Box2 regions encompass the sites of association with the Janus kinases (Jak). Jakl associates constitutively with IL-2R/> and Jak3 associates constitutively with yc. Both IL-2R/> and yc encode multiple cytoplasmic tyrosine residues with approximated locations shown. At least some of these tyrosines on both chains become phosphorylated following receptor activation whereupon they serve to recruit effector proteins to direct downstream signaling events.

The postsynaptic response to a chemical messenger appears to occur at postsynaptic active zones, which can be recognized morphologically at sites where nerve terminals make contact with other neurons or effector cells such as striated muscle. They consist of a pronounced density of intra-membranous particles as viewed under electron microscopy. These particles are at least 100-fold more enriched in active zones when compared to the remainder of the membrane. At the cholinergic nerve-muscle junction, evidence exists to suggest that these intramembranous particles are in fact ion channel—receptor complexes. Portions of the particles, thought to be the receptors, turn over with a time course of days, but the overall integrity of the active zones remains intact. In the cerebral cortex of the central nervous system, dendritic spines of neurons have been shown to be concentrated with active zones. These active zones appear to be intimately associated with portions of the neuronal cytoskeleton, since the cytoplasmic portion of the active zone displays a prominent band of fuzzy material, which, in turn, makes contact with microfilaments. 

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