Receptors are themselves subject to physiological regulation. The number of receptors a cell has (or the affinity of the receptors for their specific messenger) can be increased or decreased, at least in certain systems. An important example of such regulation is the phenomenon of down-regulation. When a high extracellular concentration of a messenger is maintained for some time, the total number of the target-cell's receptors for that messenger may decrease—that is, down-regulate. Down-regulation has the effect of reducing the target cells' responsiveness to frequent or intense stimulation by a messenger and thus represents a local negative-feedback mechanism. For example, a prolonged high plasma concentration of the hormone insulin, which stimulates glucose uptake by its target cells, causes down-regulation of its receptors, and this acts to dampen the ability of insulin to stimulate glucose uptake.
Specificity of receptors for chemical messengers. Only cell A has the appropriate receptor for this chemical messenger and, therefore, is a target cell for the messenger.
PART TWO Biological Control Systems
Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition
Change in the opposite direction (up-regulation) also occurs. Cells exposed for a prolonged period to very low concentrations of a messenger may come to have many more receptors for that messenger, thereby developing increased sensitivity to it. For example, days after the nerves to a muscle are cut, thereby eliminating the neurotransmitter released by those nerves, the muscle will contract in response to amounts of experimentally injected neurotransmitter much smaller than those to which an innervated muscle can respond.
Up-regulation and down-regulation are made possible because there is a continuous degradation and synthesis of receptors. The main cause of down-regulation of plasma-membrane receptors is as follows: The binding of a messenger to its receptor can stimulate the internalization of the complex; that is, the messenger-receptor complex is taken into the cell by endocytosis (an example of so-called receptor-mediated endocytosis); this increases the rate of receptor degradation inside the cell. Thus, at high hormone concentrations, the number of plasma-membrane receptors of that type gradually decreases.
The opposite events also occur and contribute to up-regulation: The cell may contain stores of receptors in the membrane of intracellular vesicles, and these are available for insertion into the membrane via exocyto-sis (Chapter 6).
Another important mechanism of up-regulation and down-regulation is alteration of the expression of the genes that code for the receptors.
Down-regulation and up-regulation are physiological responses, but there are also many disease processes in which the number of receptors or their affinity for messenger becomes abnormal. The result is unusually large or small responses to any given level of messenger. For example, the disease called myasthenia gravis is due to destruction of the skeletal muscle receptors for acetylcholine, the neurotransmitter that normally causes contraction of the muscle in response to nerve stimulation; the result is muscle weakness or paralysis.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.