Biological Action

FIGURE 1-4 Example of a neurohormone operating in a synapse. In the case of some amine hormones or neurotransmitters, their synthesis may be confined to the nerve ending, whereas other substances are synthesized in the cell body and transported to the nerve ending, as shown here.

1. General Considerations of Hormones chemical messengers. Thus, a neuron normally innervates a single cell. While the electrical signal of the neuron may travel a long anatomical distance over the axon, the actual electrical "message" is transformed into a chemical mediator, the neurotransmitter, which is secreted by the axon. The neurotransmitter then diffuses locally across the synapse to the adjacent receptor cell. Thus, neurotransmitters, such as acetylcholine and norepinephrine, may be thought of as paracrine hormones. An example of a neurohormone operating in a synapse is given in Figure 1-4.

D. General Concept of a Hormone Receptor

Hormones effect delivery of their "message" to target cells by interaction with a cellular constituent, namely, the receptor. All receptors have two key components: (a) a ligand-binding domain that noncova-lently but stereospecifically binds the correct hormone for that receptor and (b) an effector domain that "recognizes" the presence of the hormone bound to the ligand domain and that then initiates the generation of the biological response(s). The "recognition" process that occurs between the ligand-binding domain and the effector domain is achieved by a coupling or transduction process believed for many receptors to be an allosteric conformational change. Thus, binding of the hormone to the ligand domain results in subtle but critically important changes in the environment of the effector site, so that the signal transduction process is initiated (see Figure 1-5). The competent hormone effector site may then interact with other cellular constituents to complete the signal transduction process.

Those steroid hormone receptors that are present in the cytosolic and nuclear compartments of the cell interact with DNA. Peptide and protein hormones usually (but not always) interact with receptors present in the outer membrane of the cell. Then, depending upon the system, the hormone-receptor complex will physically interact with other cellular constituents such as G proteins (discussed later in this chapter) and /or ion channels. As a consequence of occupancy of the membrane receptor, a variety of intracellular second messengers may be generated inside the cell; these second messengers, e.g., cyclic AMP, cyclic GMP, Ca2+, diacylglycerol (DAG), inositol triphosphate (IP3), then move elsewhere inside the cell and complete the transfer of the "message" to still other cellular constituents, which then produce the biological response "signaled" by the initiating hormone.

Receptors are largely composed of proteins, but they can contain secondary modifications of carbohydrate and, in addition, may be selectively imbedded within a lipid membrane bilayer. Receptors can also become phosphorylated or myristoylated (addition

Ligand Binding Domain

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