What heppens to buprenorphine (or other opiods) after they have attached to the receptor?

Submitted by Brandis_Black1994 t3_116ydy3 in askscience

I'm very curious to know what happens, or what causes the opioid (opiate) to be removed from the receptor after it has attached and completed its job. Is there like an enzyme in the brain (not the blood or liver unless that IS the only thing that causes it to be removed FROM the receptor) or another type of chemical that plucks the opioid from the receptor and goes back into the blood/liver to be degraded by CYP450 enzymes. I'm looking for a specific chemical that detaches the opioid from the receptor. I tried searching online in many different ways even read the wiki page to no avail. Can anyone help answer this question?

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aTacoParty t1_j9b1g34 wrote

As far as I am aware there is no such molecule. Opioids, like many ligands, bind receptors in a dynamic equilibrium meaning they are constantly binding and dissociating. Some are 'stickier' than others but none of them require enzymatic removal. The life cycle of the drug starts with high concentrations in your blood soon after taking it. It then diffuses down its concentration gradient into various tissues including the CNS where it binds mu opioid receptors to create an analgesic effect. As the liver removes it from the blood, the concentration gradient gets reversed with higher concentrations in the tissues and lower in the blood. So it once again diffuses down the concentration gradient back into the blood system where it gets removed.

Receptors may get endocytosed by neurons to prevent continued activation, but this doesn't necessarily remove the opioid from the receptor, it just prevents downstream signaling.

Dissociation of opioids from receptors (computation modeling)

https://pubs.acs.org/doi/10.1021/jacsau.1c00341

Endocytosis of opioid receptors after activation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683597/

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randomEODdude t1_j9asl0d wrote

The answer your looking for is most likely GTP. Opioid receptors are g coupled protein receptors (GCPR) which. Understanding this mechanism requires a basic understanding of biochemistry and the central dogma of molecular biology. But you can think of GTP as a molecule that does work. So the opioid binds, causes a change on the other end of the protein receptor, which leads to downstream effects and ends when GDP is replaced by GTP, causing a conformational change in the GPCR, releasing the opioid.

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