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What Are Opioid Receptors?

By Christina Hall
Updated May 17, 2024
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An opioid receptor is a G protein-coupled receptor, where the activation of a protein on the outside of a cell activates a cascade of chemical pathways within the cell. Opioid receptors are molecules, or sites, within the body that are activated by opioid substances. These sites were discovered in the early 1970s during research into how opiate medications exert their action within the human body. Opioid receptors are found in abundance in the spinal cord, but are also found in in lower concentrations in places like the digestive tract. There are many opiate substances that are capable of activating the receptor sites, including endogenous opioids made by the human system, like endorphins and enkephalins, as well as external laboratory-made opiates, like hydrocodone and morphine.

Opioid receptors inhibit the transmission of impulse in excitatory pathways within the human body system. These pathways include the serotonin, catecholamine, and substance P pathways, which are all implicated in pain perception and feelings of well-being. Opioid receptors are further subclassified into mu, delta, and kappa receptors. All the classes, while exhibiting differing modes of action, share some basic similarities. They all are driven by the potassium pump mechanism, which is found on the plasma membrane of the majority of cells.

The differing action seen by the mu, delta, and kappa designations is not so much due to varied cellular responses after the potassium pump is activated, but due to the anatomical placement of the receptors. For example, opiate receptors that are located on the spinal cord and in the brain exhibit a pain-dampening effect in the central nervous system, whereas opiate receptors in the respiratory and digestive tracts inhibit other actions like digestion and the cough response. The inhibitory response is activated in all opioid receptors beginning with the inhibition of a common enzyme, adenylate cyclase. The subsequent chemical cascade after this initial chemical reaction reduces the flow of related information to the processing centers within the brain. People suffering from opiate medication withdrawal do not have enough opiate substance to inhibit these excitatory pathways, leading to agitation and an exaggerated pain response.

Much of the research that has been done on opioid receptors focuses specifically on the mu receptor. Stimulation of this receptor is associated with intense feelings of euphoria and serenity. This reaction is thought to be due, in part, to the mu receptor’s cross reaction with the dopamine and gamma-amino butyric acid (GABA) neurotransmitter systems. The body produces an opioid substance that is similar to the mu receptor-bound narcotic, morphine.

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