Orphan endogenous lipids and orphan GPCRs: a good match.
A large and growing family of over 70 endogenous lipids of the basic structure N-acyl amide has been identified during the last 10 years. Only a few of these lipids have been characterized for biological activity, however, those that have shown a wide-range of activity may act at G-protein coupled receptors (GPCRs). Like orphan GPCRs that are identified as being in the genome and expressed in tissue, the majority of these endogenous lipids many produced throughout the body, some predominately in nervous tissue, remain orphaned. Here, we give a brief history of these orphan lipids and highlight the activity of N-arachidonoyl glycine, and farnesyl pyrophosphate at the orphan receptors GPR18 and GPR92, respectively, as well as summarizing the biological and pharmacological data for the recently identified N-palmitoyl glycine that suggests activity at a novel GPCR. Working to deorphanize both lipids and GPCRs together provides a unique opportunity for a greater understanding of cellular signaling and a challenge to find them all a home.
Bradshaw
Heather B
HB
The Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA. hbbradsh@indiana.edu
Lee
Sung Ha
SH
McHugh
Douglas
D
D000577:Amides / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology*; D010169:Palmitic Acids; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology; D012107:Research Design; D012717:Sesquiterpenes / Q000378:metabolism; D015398:Signal Transduction
D000577:Amides; D005227:Fatty Acids; C107515:GPR18 protein, human; C512992:LPAR5 protein, human; D008055:Lipids; D010169:Palmitic Acids; D011106:Polyisoprenyl Phosphates; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D012717:Sesquiterpenes; C095773:N-palmitoylglycine; C004808:farnesyl pyrophosphate; D005998:Glycine