Biased signaling by endogenous opioid peptides
Abstract
There are >20 different endogenous opioid peptides derived from the three precursors proopiomelanocortin, proenkephalin, and prodynorphin; a long-standing question is the biological utility of having this variety of peptides. We addressed this question by systematically evaluating ligand binding and signaling properties of the peptides at each of the three opioid receptor types. Contrary to the prevailing notion, we show that all of the peptides bind and activate the three opioid receptors and that shorter β-endorphin peptides exhibit agonistic activity. Finally, we demonstrate that some endogenous peptides favor particular signaling pathways at the three receptors leading to biased signaling. These findings highlight the complexity of signaling where multiple opioid receptors are expressed and/or many opioid peptides are released.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 11, 2020
- Source ID
- 10.1073/pnas.2000712117
Entities
People
- Achla Gupta
- Brian M Cox
- Elyssa B. Margolis
- Ivone Gomes
- Lakshmi A Devi
- Lindsay Lueptow
- Salvador Sierra
- Shawn Gouty
Organizations
- Icahn School of Medicine at Mount Sinai
- National Institute of Neurological Disorders and Stroke
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- Uniformed Services University of the Health Sciences
- United States Department of Defense
- University of California, Los Angeles
- University of California, San Francisco
- Virginia Commonwealth University