Introduction
In the first two articles of “Fun with Physiology,” we addressed how electrolytes such as sodium, potassium, calcium, magnesium, and chloride affect cellular action potentials. If you have not read these articles, I would recommend doing so because they are the foundational concepts from which this entire series is founded. This month’s article will look at the relationship between receptors and how they influence cellular function.
Receptor Theory
Cells within our bodies have specific functions depending upon the system they are associated with. Cardiac cells are associated with heart function, brain cells with thought and cognition, skeletal muscle cells with movement, and so forth. Most cells are unable to initiate their action unless they are signaled to do so. This is where receptors come into play.
Receptors are protein structures that either span the cell membrane or are located inside the cell. Receptors are responsible for processing signals and initiating cellular functions. Without stimulating these receptors, cells would not be signaled to initiate their specific function. This means cardiac cells would not create a heartbeat, brain cells would have no thought and cognition, and skeletal muscles would not move the body…
The term “receptor theory” is used to explain how medications interact with cellular receptors. It is important to understand our bodies naturally produce substances that also stimulate these receptors. For the sake of this article, we will be addressing any substance whether natural or man-made that affects a receptor.
Receptors
The role of a receptor is to signal the cell to initiate its intended function. For all intents and purposes, a receptor is either signaling or not signaling. There is rarely an in-between signaling state for most cellular receptors. When a receptor is signaling, this is referred to as an active state. An inactive state is when the receptor is not signaling.
There are four major types of receptors:
- Ion channel receptors
These receptors are associated with the movement of ions/electrolytes. Functions of the primary ions/electrolytes have been illustrated through the School House Theory in the first two articles within this series.
- G protein-coupled receptors
G protein receptors are the most abundant receptors within the body. Approximately 34% of pharmaceutical medications approved by the FDA focus on influencing this receptor group3.
- Enzyme-linked receptors
These receptors stimulate changes with intracellular enzymes. They are also referred to as catalytic receptors.
- Intracellular receptors
Intracellular receptors are located inside the cell and tend to influence changes within the nucleus (control center) of the cell.
At this point and time, it is not necessary to differentiate between these four types of receptors. It is important to understand that signaling a receptor will result in activation of a cell’s action, and inhibiting a signal diminishes the action of a cell.
Receptor Confirmation
Receptors exist in equilibrium between active and inactive states. A ligand (‘ligәnd) is a naturally produced substance, and/or medication that signals a receptor. An agonist is a ligand that signals a receptor into an active state. Once the receptor is signaled by a ligand, the associated stimulation initiates its cellular action. When a receptor achieves active state, this is referred to as an active receptor confirmation.
An antagonist is a ligand that stimulates a receptor, but the level of stimulation is significantly less than an actual agonist. This prevents the receptor from being stimulated to a level that achieves an active state. This diminishes the cell’s ability to initiate its intended function.
Receptor Signaling
For illustration’s sake, we will refer back to the cell as a schoolhouse. For physiology to occur, the schoolhouse needs to be signaled to initiate its intended function. In this illustration, think of a receptor as the principal of the school who needs to receive the signal from a ligand to initiate the school’s function. The ligand is a messenger who needs to deliver the signal to the principal who then initiates the school’s function. There are three basic ways a ligand signals the principle to initiate the school’s function:
- Ligand has a key to the front door.
By being able to unlock the front door the ligand can directly deliver the signal to the principal who then initiates the school’s function.
- Ligand rings the doorbell.
This ligand doesn’t have a key to the front door but is able to ring the doorbell to signal the principal to initiation the school’s function.
- Ligand has a radio to communicate with the principal inside the schoolhouse.
This ligand doesn’t have a key to the front door, nor an ability to ring the doorbell. It does have a radio that directly communicates to the principal inside the school.
As mentioned, there are ligands that inhibit the ability of the principal to receive a signal to initiate the school’s function. These are referred to as an antagonistic ligand. Think of these ligands as individuals who are holding protest signs and radio jammers that squat themselves on the front doorsteps of the school. If these protestors are squatting on the doorstep, they prevent the messenger from delivering their signal to the principal of the school. This inhibition will ultimately result in a diminished level of functionality for the cell.
Receptor Theory for EMS
Understanding receptor theory provides EMS personnel with a deeper understanding of what may be causing their patients to present with specific clinical findings. This is especially true if the patient is suffering from a medical condition or conditions which over signal or under signal cellular receptors. This is also the first step in understanding how medications influence human physiology and pathophysiology.
There are multiple ways cells can increase or decrease their ability to control physiologic functions. These physiologic functions revolve around many different factors. Receptors play a significant role in how a cell will either initiate its function or inhibit its function. For those of you interested, follow this link to view a video describing the concepts that are illustrated within this article: https://www.youtube.com/watch?v=za6DM687BaM.
References
- Adams, M., (2017) Pharmacology for Nurses A Pathophysiologic Approach. New York, NY: Pearson.
- Giraldo, J., (2004) Agonist Induction, Confirmational Selection, and Mutant Receptors. FEBS Press. 556 (1-3):8-13.
- Hauser, A., Sreenivas, C., Ikuo, M., Leoni, J., Kirill, M., David, G., Madan Babu, M., (2018) Pharmacogenomics of GPCR Drug Targets. Cell. 172(1-2):41-54.
- Kenakin, T., (2004) Principles: Receptor Theory in Pharmacology. Trends in Pharmacological Science. 25:4.
- Kenakin, T., (2008) What Systems Can and Can’t Do. British Pharmacological Society. 153(5):841-843.
- Limbird, L.E., (2004) The Receptor Concept: a Continuing Evolution. Molecular Interventions. 4 (6):326-336.
- Maehle, A.H., Prull, C.R., Halliwell, R.F., (2002) The Emergence of the Drug Receptor Theory. Nature Review Drug Discovery. 1 (8):637-641.