Thursday, 23 January 2020

What are receptors?


Receptors are very important for cell signaling and other function in this article we are introducing various types of receptors and their functions. These messengers include molecules such as neurotransmitters and paracrine substances, whose signals are mediated rapidly and over a short distance. Other messengers, such as hormones, communicate over greater distances and in some cases, more slowly. Whatever the chemical messenger, however, the cell receiving the signal must have a way to detect the signal’s presence. Once a cell detects a signal, a mechanism is required to transduce that signal into a physiologically meaningful response, such as the cell division response to the delivery of growth-promoting signals.

The first step of the action of any intercellular messenger to the specific chemical messenger is the binding of target-cell proteins are known or receptor proteins. The sequence of events in the cell leading to the cell’s response to that messenger, a process called signal transduction. In this section, we consider general features common to many receptors, describe interactions between receptors and their ligands, and give some examples of how receptors are regulated.

Types of Receptors

What is the nature of the receptors that bind intercellular chemical messengers? They are proteins or glycoproteins located either in the cells' plasma membrane inside the cell, either in the cytosol or the nucleus. The plasma membrane is the much more common location because a very large number of messengers are water-soluble and therefore cannot diffuse across the lipid-rich (hydrophobic) plasma membrane. In contrast, a much smaller number of lipid-soluble messengers diffuse through membranes to bind to their receptors located inside the cell.

Plasma Membrane Receptors A typical plasma membrane receptor is illustrated Plasma membrane receptors are transmembrane proteins; that is, they span the entire membrane thickness. Like other transmembrane proteins, a plasma membrane receptor has hydrophobic segments within the membrane, one or more hydrophilic segments extending out from the membrane into the extracellular fluid, and other hydrophilic segments extending into the intracellular fluid. Arriving chemical messengers bind to the extracellular parts of the receptor; the intracellular regions of the receptor are involved in signal transduction events.

Intracellular Receptors, By contrast, intracellular receptors are not located in membranes but exist in either the cytosol or the cell nucleus and have a very different structure. Like plasma membrane receptors, however, they have a segment that binds the messenger and other segments that act as regulatory sites. This is one key distinction between the two general types of receptors; plasma membrane receptors can transduce signals without interacting with DNA, whereas all intracellular receptors transduce signals through interactions with genes.

(a)Intracellular Receptors

Intracellular Receptors

Figure .1  The two major classes of receptors for chemical messengers. 
(a) Structure of a typical transmembrane receptor. The seven clusters of amino acids embedded in the phospholipid bilayer represent hydrophobic portions of the protein’s alpha-helix (shown here as cylinders). Note that the binding site for the hormone includes several of the segments that extend into the extracellular fluid. Portions of the extracellular segments can be linked to carbohydrates (CHO). The amino acids denoted by black circles represent some of the sites at which intracellular enzymes can phosphorylate, and thereby regulate, the receptor. 
(b) Schematic representation of the structural features of a typical nuclear receptor. The actual structures for segments of these receptors are known and are shown here for the human estrogen (a steroid hormone) receptor. (Note The segments of proteins—including those of nuclear receptors—that perform different functions are known as “domains.”)

However, the competing molecules are different enough in structure from the native ligand that, although they bind to the receptor, they cannot activate it. This blocks the endogenous messenger from binding and yet does not induce signal transduction or trigger the cell’s response. The general term for a compound that blocks the action of a chemical messenger is the antagonist; when an antagonist works by competing with a chemical messenger for its binding site, it is known as a competitive antagonist. Certain antihistamines are competitive antagonists that block histamine from binding to its receptors on mast cells and triggering an allergic response.

Some drugs that compete with natural ligands for a particular receptor type do activate the receptor and trigger the cell’s response exactly as if the true (endogenous) the chemical messenger had combined with the receptor. Such drugs, known as agonists, are used therapeutically to mimic the messenger’s action. For example, the common decongestant drugs phenylephrine and oxymetazoline, found in many types of nasal sprays, mimic the action of epinephrine on a related but different subtype of receptors, called alpha-adrenergic receptors, in blood vessels. When alpha-adrenergic receptors are activated, the smooth muscles of inflamed, dilated blood vessels in the nose contract, resulting in narrowing of those vessels; this helps open the nasal passages and decrease fluid leakage from blood vessels.

Regulation of Receptors

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 in certain systems. When the 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—that is, desensitizing them—and thus represents a local negative feedback mechanism.

Down-regulation is possible because there is a continuous synthesis and degradation of receptors. The main mechanism of down-regulation of plasma membrane receptors is internalization. This increases the rate of receptor degradation inside the cell. Consequently, at increased messenger concentrations, the number of plasma membrane receptors of that type gradually decreases during down-regulation.

Change in the opposite direction, called up-regulation, also occurs. Cells exposed for a prolonged period to very low concentrations of a messenger may come to have many more receptors that messenger, thereby developing increased sensitivity to it.

The greater the number of receptors available to bind a ligand, the greater the likelihood that such binding will occur. For example, when the nerves to a muscle are damaged, the delivery of neurotransmitters from those nerves to the muscle is decreased or eliminated. With time, under these conditions, the muscle will contract in response to a much smaller amount of neurotransmitter than normal. This happens because the receptors for the neurotransmitter have been up-regulated, resulting in increased sensitivity.

Interactions Between Receptors and Ligands

There are four major features that define the interactions between receptors and their ligands: specificity, affinity, saturation, and competition. Specificity The binding of a chemical messenger to its receptor initiates the events leading to the cell’s response. This is
generally the case for chemical messengers and their receptors.

Specificity This is because cells differ in the types of receptors they possess. Only certain cell types—sometimes just one—express the specific receptor required to bind a given chemical messenger. In the case where many different cell types possess receptors for the same messenger, however, the responses of the various cell types messenger may differ from each other. For example, the neurotransmitter norepinephrine causes muscle cells of the heart to contract faster but, via the same type of receptor, regulates certain aspects of behavior by acting on neurons in the brain.

Just as identical types of switches can be used to turn on a light or a radio, a single type of receptor can be used to produce different responses to the same chemical messenger in different cell types.

Affinity The remaining three general features of ligand-receptor interactions are summarized of differences in the affinity of receptors for their ligands have important implications for the use of therapeutic drugs in treating illness; receptors with high affinity for a ligand requires much less of the ligand (that is, a lower dose) to become activated.

Saturation The phenomenon of receptor saturation as described or ligands binding to binding sites on proteins, and are fully applicable here. A cell’s response messenger increases the extracellular the concentration of the messenger increases, because of the number of receptors occupied by messenger molecules increases. There is an upper limit to this responsiveness, however, because only a finite number of receptors are available, and they become fully saturated at some point.

Competition refers to the ability of a molecule to compete with a natural ligand for binding to its receptor. The competition typically occurs with messengers that have a similarity in part of their structures and it also underlies the action of many drugs. If researchers or physicians wish to interfere with the action of a particular messenger, they can administer competing molecules that are structurally similar enough to the endogenous messenger that they bind to the receptors for that messenger.


Figure .2  Specificity of receptors for chemical messengers.
Only cell A has the appropriate receptor for this chemical messenger; therefore, it is the only one among the group that is a target cell for the messenger.


Figure.3  Characteristics of receptors binding to messengers. The receptors with high affinity will have a more bound messenger at a given messenger concentration (e.g., concentration X). The presence of a competitor will decrease the amount of messenger bound, until at very high concentrations the receptors become saturated with messenger

and cannot bind any additional messenger. Note in the illustration that the low-affinity receptor, in this case, has a slightly different shape in its ligand-binding region compared to the high-affinity receptor, which makes it less able to bind the messenger. Also, note the similarity in parts of the shapes of the natural messenger and its competitor.

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