The endogenous system of opioid receptors (μ MOR,κ KOR, and, δ DOR) is well known for its analgesic potential, but each receptor initiates different effects.
Below are quick descriptions of each:
MOR can mediate acute changes in neuronal excitability via suppression of presynaptic release of GABA.
Activation of the μ-opioid receptor by an agonist such as morphine causes
- slightly reduced blood pressure,
- decreased respiration,
- miosis (constricted pupils), and
- decreased bowel motility often leading to constipation.
Other areas where they have been located include
- the external plexiform layer of the olfactory bulb,
- the nucleus accumbens,
- in several layers of the cerebral cortex, and
- in some of the nuclei of the amygdala, as well as the nucleus of the solitary tract.
Some MORs are also found in the intestinal tract. Activation of these receptors inhibits peristaltic action which causes constipation, a major side effect of μ agonists
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is a 7-transmembrane G-protein coupled receptor, that has enkephalins as its endogenous ligands.
The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model.
In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain; the basal ganglia, which is heavily GABA populated, has been linked to major depressive disorder, suggesting a possible role for the δ-opioid receptor in mood modulation.
The exact role of δ-opioid receptor activation in pain modulation is largely up for debate.
Activation of δ receptors produces analgesia, much more significantly than that of mu-opioid agonists.
However, it seems like mu agonism provides heavy potentiation to any δ-opioid receptor agonism.
It is also suggested however that the pain modulated by the mu-opioid receptor and that modulated by the δ-opioid receptor are distinct types, with the assertion that DOR modulates the nociception of chronic pain, while MOR modulates acute pain.
The KOR may provide a natural addiction control mechanism, and therefore, drugs that act as agonists and increase activation of this receptor may have therapeutic potential in the treatment of addiction
Below is how receptor bindings function:
Not every ligand that binds to a receptor also activates that receptor. The following classes of ligands exist:
- (Full) agonists are able to activate the receptor and result in a strong biological response. The naturalendogenous ligand with the greatest efficacy for a given receptor is by definition a full agonist (100% efficacy).
- Partial agonists do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared to those of full agonists (efficacy between 0 and 100%).
- Antagonists bind to receptors but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. Receptor antagonists can be competitive (or reversible), and compete with the agonist for the receptor, or they can be irreversible antagonists that form covalent bonds (or extremely high affinity non-covalent bonds) with the receptor and completely block it. The proton pump inhibitor omeprazole is an example of an irreversible antagonist. The effects of irreversible antagonism can only be reversed by synthesis of new receptors.
- Inverse agonists reduce the activity of receptors by inhibiting their constitutive activity (negative efficacy).
- Allosteric modulators: They do not bind to the agonist-binding site of the receptor but instead on specific allosteric binding sites, through which they modify the effect of the agonist. For example,benzodiazepines (BZDs) bind to the BZD site on the GABAA receptor and potentiate the effect of endogenous GABA.
Note that the idea of receptor agonism and antagonism only refers to the interaction between receptors and ligands and not to their biological effects.