How an orphan receptor became the key to improving brain connections

Since 1999, scientists have been trying to find the key to unlock the brain nerve receptor known as GPR158. In a study published in Science this week, the so-called orphan receptor’s unlocking molecule has been announced and so has its new name. 

How It Works

Freshly introduced as mGlyR, the receptor–formerly known as GPR158–has been proven to work hand in hand with an amino acid called glycine to change the speed of beneficial changes in the brain.

The study was conducted by a team of researchers from the Scripps Research Institute in Florida. The team led by Kirill Martemyanov used gene expression analysis, receptor binding assays, and functional studies to ultimately identify glycine as the missing link to mGlyR’s importance to mental wellness.

The study showed that mGlyR is a metabotropic receptor, which means that it sends signals slowly. When glycine binds to mGlyR, it slows the activity of another protein called RGS7-Gβ5. RGS7-Gβ5 is a protein that slows the production of a second messenger called adenosine 3′,5′-monophosphate (AMP). When AMP levels are low, it leads to fewer beneficial metabolic processes in the brain. By slowing the activity of RGS7-Gβ5, glycine acts on mGlyR to “slow down the slow downer” so the benefits of AMP can increase.

The discovery of mGlyR as a glycine receptor could have important implications for understanding and treating a variety of neurological disorders. For example, the study suggests that mGlyR may play a role in depression, anxiety, and other mood disorders. 

A Common Remedy

While more research is needed to investigate the role of mGlyR in these and other mental health problems, the newly discovered function of glycine explains much about the longstanding use of magnesium glycinate in integrative psychiatry.

Magnesium glycinate is a form of magnesium that is bound to the amino acid glycine. It is one of the most bioavailable forms of magnesium, meaning that it is easily absorbed by the body. Magnesium glycinate has a number of benefits, including:

  • Improved sleep: Magnesium glycinate is a natural sleep aid. It helps to relax the body and mind, making it easier to fall asleep and stay asleep.
  • Reduced anxiety: Magnesium glycinate is also effective at reducing anxiety. It helps to calm the nervous system and promote feelings of relaxation.
  • Improved mood: Magnesium glycinate can also help to improve mood. It helps to regulate serotonin levels, which are important for mood balance.
  • Reduced muscle tension: Magnesium glycinate is a good source of magnesium, which is an essential mineral for muscle relaxation. It can help to reduce muscle tension and pain.
  • Improved cognitive function: Magnesium glycinate can also help to improve cognitive function. It helps to improve memory, focus, and concentration.

Final Thoughts

The discovery of the effect of glycine on mGlyR suggests that magnesium glycinate may be even more beneficial than previously thought. It is a promising natural remedy for a variety of conditions, and it is safe and well-tolerated by most people.

Laboute, T., Zucca, S., Holcomb, M., Patil, D.N., Garza, C., Wheatley, B.A., Roy, R.N., Forli, S., & Martemyanov, K.A. (2023). Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. Science, 379(6639), 1352-1358. doi: 10.1126/science.add7150