Orphan endogenous lipids and orphan GPCRs: a good match

Area of Science:

• Biochemistry
• Pharmacology
• Neuroscience

Background:

• Over 70 N-acyl amide endogenous lipids identified in the last decade.
• Most of these lipids and their biological targets, orphan G-protein coupled receptors (GPCRs), remain uncharacterized.
• Lipids are produced throughout the body, with some concentrated in nervous tissue.

Purpose of the Study:

• To provide a historical overview of orphan lipids.
• To highlight the activity of specific lipids (N-arachidonoyl glycine, farnesyl pyrophosphate, N-palmitoyl glycine) at orphan GPCRs.
• To deorphanize lipids and GPCRs for a better understanding of cellular signaling.

Main Methods:

• Literature review of endogenous lipids and GPCRs.
• Summary of biological and pharmacological data for key lipids.
• Focus on identifying novel GPCR activity for N-palmitoyl glycine.

Main Results:

• N-arachidonoyl glycine shows activity at the orphan receptor GPR18.
• Farnesyl pyrophosphate acts at the orphan receptor GPR92.
• N-palmitoyl glycine suggests activity at a novel GPCR.

Conclusions:

• Deorphanizing lipids and GPCRs simultaneously offers a unique research opportunity.
• Understanding these interactions is crucial for advancing cellular signaling knowledge.
• The goal is to fully characterize the roles of these lipid-GPCR pairs.