1. Welliver, Mark DNP, RN, CRNA
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Receptors are proteins embedded within the lipid cell membranes of our body's tissues. Receptors are composed of varying arrangements of amino acids. Amino acid sequence (expression) is dictated by deoxyribonucleic acid (DNA) coding. DNA, the master code of cell replication, dictates the creation of all receptors. Receptors reside interspersed within the lipid bilayer membrane of cells.


On a microscopic level, the lipid membrane is a broad expanse of a double layer of amphiphilic molecules. Amphiphilic molecules are those that contain both a charged water-soluble (hydrophilic) end and an uncharged fat-soluble (lipophilic) end. The lipid bilayer is composed of two planes of amphiphilic molecules arranged so that their water-soluble ends point outward while the lipophilic tails are attached in the center of the two planes (Figure 1).

Figure 1 - Click to enlarge in new windowFIGURE 1. Amphiphilic lipid bilayer.

Interspersed in this broad lipid field are protein molecules that transect the lipid membrane (Figure 2). Imagine a grass field with tulips. The green blades of grass represent the tightly connected lipid molecules. Interspersed among these blades are tulip flowers representing the protein receptors. Many different colored tulips represent many different protein receptor types. The petals of a tulip are much like the protrusions of a receptor. Receptors may have two or more "petals," and within their center a tube or channel is formed (Figure 3). Much like the stimulation of the sun will open the tulips petals, so too will a particular molecule (i.e., neurotransmitter, drug) cause the receptor to open or close. This conceptual representation of the cellular membrane landscape as a field of grass interspersed with tulip "receptors" allows continued focus of a complex system while maintaining this simplified analogy.

Figure 2 - Click to enlarge in new windowFIGURE 2. Protein receptors embedded within lipid bilayer.
Figure 3 - Click to enlarge in new windowFIGURE 3. Protein receptor showing central channel in closed and open positions.

The receptor, much like a tulip, has three basic parts: (a) the petals protruding above the lipid membrane, (b) the stems located within the lipid membrane, and (c) the base or roots located just below the lipid membrane. The opening of the petals allows for a channel to be created through the stem and into the area below the lipid membrane.


Activation of the receptor causes the amino acid strands to move (Figure 4). This is called a conformational change; the form of the receptor actually changes. The activation of a receptor is described as a lock-and-key mechanism as only certain molecules, usually a neurotransmitter, may cause an effect (Figure 5). The specific "fit" of a molecule onto the receptor may occur anywhere.

Figure 4 - Click to enlarge in new windowFIGURE 4. Receptor closed position.
Figure 5 - Click to enlarge in new windowFIGURE 5. Lock-and-key mechanism causing opening of channel.

Sometimes, several "keys" (molecules, drugs, or toxins) may activate a receptor by attaching at several different locations (Figure 6). Often, the stronger a key's attachment to a receptor the greater its effect will be. This is especially true for drugs. A drug with greater attachment strength (affinity) for a receptor will exert greater or prolonged effect compared with a drug with lesser affinity. Once a drug or molecule attaches to a receptor, the conformational (shape) change may open or close a receptor's central channel or pore (Figures 5 and 6). The channel may then allow passage of other substances or cause other substances already in the cell to perform a specific cell function.

Figure 6 - Click to enlarge in new windowFIGURE 6. Multiple drugs attaching at multiple sites causing channel opening. A, B, and C represent multiple drug attachment sites that may cause channel opening.

Drug Binding to Receptors

A molecule, often a drug, binds to a receptor based on its steric nature. In short, a drug's geometric shape along with its electron distribution of energies must match some part of the receptor's geometric shape and its energy distribution for an affinity (attraction) to occur. Molecules do not fit together based solely on the shape, but rather their energy distributions that attract, repel, or have no effect. Much like two magnets that attract or repel based on their orientation of electromagnetic interactions, so too are molecules pulsating structures of energy distribution. If part or all of a molecule is attracted to part of a receptor based on these energy attractions, then binding may occur. The greater the fit (attraction) of these energies, the more pronounced the effect or duration would be. It is important to reiterate that a molecule or drug that binds to a receptor may activate or inactivate it. A drug that activates a receptor is called an agonist. A drug that inactivates a receptor is called an antagonist.


Although not all drugs act on receptors, many do and knowledge of receptor theory aids in understanding drug action and effect. General rules may apply to drugs that work on receptors:


* A drug with high affinity for a receptor will have higher potency than a drug with less affinity.


* Higher dose will be needed for a drug with lower receptor affinity compared with a drug with higher affinity.


* Receptors tend to increase their numbers (upregulate) when exposed to long-term administration of antagonists.


* Receptors tend to decrease their numbers (downregulate) when exposed to long-term administration of agonists.


* Slight variations in receptor gene expression may cause increased, decreased, altered, or unexpected drug reactions in some individuals.



Receptor theory lends itself to a better understanding of the mechanism of action of many drugs. Receptor theory also allows one to better focus on causes and treatments for particular ailments or symptoms. For gastroenterology nurses, nausea and vomiting are particular patient concerns. Although the causes of nausea and vomiting are vast, only a few receptors are directly responsible for these symptoms. Targeting the underlying cause and specific receptors associated with nausea and vomiting improves the treatment. Future columns will take a focused exploration of the neuronal and receptor mediated causes of nausea and vomiting as well as specific antiemetic drugs.




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Ross E. M., Kenakin T. P. (2001). Pharmacodynamics. Mechanisms of drug action and the relationship between drug concentration and effect. In Hardman J. G., Limbird L. E. (Eds.), Goodman & Gilman's the Pharmacological Basis of Therapeutics (pp. 31-43). Vol. 10. New York, NY: McGraw-Hill.


Ruffolo R. R. Jr. (1982). Important concepts of receptor theory. Journal of Autonomic Pharmacology, 2(4), 277-295.