Genetic behavioral screen identifies an orphan anti-opioid system

Comment; So now we’ve found naturally occuring “brakes” to the µ mu receptor which causes analgesia & euphoria and being naturally occuring in our brains. What can we do with this?

1. Dandan Wang¹, 
2. Hannah M. Stoveken¹, 
3. Stefano Zucca¹, 
4. Maria Dao¹, 
5. Cesare Orlandi¹, 
6. Chenghui Song¹,*, 
7. Ikuo Masuho¹, 
8. Caitlin Johnston¹, 
9. Karla J. Opperman¹, 
10. Andrew C. Giles¹, 
11. Matthew S. Gill², 
12. Erik A. Lundquist³, 
13. Brock Grill¹,†, 
14. Kirill A. Martemyanov¹,†

 See all authors and affiliations

Science  15 Aug 2019:

Abstract

Opioids target the μ-opioid receptor (MOR) to produce unrivaled pain management but their addictive properties can lead to severe abuse. We developed a whole animal behavioral platform for unbiased discovery of genes influencing opioid responsiveness. Using forward genetics in C. elegans, we identified a conserved orphan receptor, GPR139, with anti-opioid activity. GPR139 is coexpressed with MOR in opioid-sensitive brain circuits, binds to MOR and inhibits signaling to G proteins. Deletion of GPR139 in mice enhanced opioid-induced inhibition of neuronal firing to modulate morphine-induced analgesia, reward, and withdrawal. Thus, GPR139 could be a useful target for increasing opioid safety. These results also demonstrate the potential of C. elegans as a scalable platform for genetic discovery of GPCR signaling principles.

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Dr. Raymond Oenbrink

Dr. Raymond Oenbrink DO is board certified by the American Osteopathic Board of Family Physicians (AOBFP) and the American Board of Addiction Medicine (ABAM). He specializes in complex and chronic illnesses such as Chronic Inflammatory Response Syndrome (CIRS).

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