This brief overview of the location and function of cannabinoid receptors in the human body provides an introduction to the endocannabinoid system and its functions. Although brief and a decade old, it does cover much of what is known about cannabinoid receptors and the implications of their distribution and function.
The short time since the discovery of the endocannabinoid system has lead to the knowledge and technology used to discover the location and purpose of cannabinoid receptors. Although the mapping of CB1 receptors is relatively complete, CB2 receptors keep appearing in places like the brain where they had not been believed to be.
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The purpose of a cannabinoid receptor seems to depend a lot on its location. The almost ubiquity of the cannabinoid receptors and the wide range of effects obtainable by cannabinoid administration has led to the discoveries of many different processes that cannabinoid receptors are involved in. The author demonstrates that the way that cannabinoids interact and where they interact can have a wide range of powerful yet subtle effects.
Where a cannabinoid receptor is located is thought to decide what its purpose is. Instead of being a specific receptor for a specific task, the current thinking is that cannabinoid receptors are more generalized than some other systems. This would account for their presence in so many different tissues.
The CB1 receptor was the first to be discovered and is largely found in the central nervous system (the brain and spine). THC is psychoactive because it activates CB1 receptors in the brain, altering signalling processes. CB1 receptors are also found in the peripheral nervous system in considerable numbers, as well as in fatty tissue, the pancreas, and skeletal muscle.
The CB2 receptor is largely found in the immune system, and at the time of writing was only theorized to be present in the central nervous system. Although they are both largely expressed in different tissues, they seem to have a coupled regulatory role in many processes.
Both CB1 and CB2 receptors are primarily G-protein coupled signalers, controlling the release of G-proteins, which act as inhibitors in a variety of functions, including calcium channels, kinases, and potassium channels.
Each cannabinoid has a different affinity to its receptor and a different shape that changes how it interacts. The differences in binding strength and shape subtly alter the way the receptor signals. This is functional selectivity and allows for greater precision in altering signalling thresholds.
An agonist binds to a receptor. A reverse agonist does the same but has the opposite effect when bound to that receptor. Partial agonists have a low affinity for their receptor, and so exert a lesser effect. Some cannabinoids are full agonists for one receptor and not the other, or partial for both.
Combined with the subtlety and precision that functional selectivity and locus brings, it is easier to see how a few simple cannabinoids can exert such a plethora of interactions, regulatory activities, and important functions.
In this assessment of the location and function of cannabinoid receptors, the importance of where they are placed is highlighted. The paper adequately describes the necessity of different forms of agonism and selectivity, and how the complexity of this system can be produced from some simple elements.