Skip to main content
Log in

Targeted lipidomics: Discovery of new fatty acyl amides

  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

The discovery of endogenous fatty acyl amides such asN-arachidonoyl ethanolamide (anandamide),N-oleoyl ethanolamide (OEA), andN-arachidonoyl dopamine (NADA) as important signaling molecules in the central and peripheral nervous system has led us to pursue other unidentified signaling molecules. Until recently, technical challenges, particularly those associated with lipid purification and chemical analysis, have hindered the identification of low abundance signaling lipids. Improvements in chromatography and mass spectrometry (MS) such as miniaturization of high-performance liquid chromatography components, hybridization of multistage mass spectrometers and time-of-flight technology, the development of electrospray ionization (ESI) and of information-dependent acquisition, now permit rapid identification of novel, low abundance, signaling lipids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.Science. 1992;258:1946–1949.

    Article  CAS  PubMed  Google Scholar 

  2. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.Biochem Pharmacol. 1995;50:83–90.

    Article  CAS  PubMed  Google Scholar 

  3. Huang SM, Bisogno T, Trevisani M, et al. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors.Proc Natl Acad Sci USA. 2002;99:8400–8405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Huang SM, Bisogno T, Petros TJ, et al. Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain.J Biol Chem. 2001;276:42639–42644.

    Article  CAS  PubMed  Google Scholar 

  5. Bradshaw HB, Walker JM. The expanding field of cannabimimetic and related lipid mediators.Br J Pharmacol. 2005;144:459–465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Elphick MR, Egertova M. The neurobiology and evolution of cannabinoid signalling.Philos Trans R Soc Lond B Biol Sci. 2001;356:381–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Piomelli D. The molecular logic of endocannabinoid signalling.Nat Rev Neurosci. 2003;4:873–884.

    Article  CAS  PubMed  Google Scholar 

  8. Mackie K. Cannabinoid receptors as therapeutic targets.Annu Rev Pharmacol Toxicol. 2006;46:101–122.

    Article  CAS  PubMed  Google Scholar 

  9. Walker JM, Huang SM. Cannabinoid analgesia.Pharmacol Ther. 2002;95:127–135.

    Article  CAS  PubMed  Google Scholar 

  10. Bradshaw HB, Rimmerman N, Krey JF, Walker JM. Sex and hormonal cycle differences in brain levels of pain-related cannabimimetic lipid mediators.Am J Physiol Regul Integr Comp Physiol [serial online]. 2006;Mar.

  11. Croxford JL, Yamamura T. Cannabinoids and the immune system: potential for the treatment of inflammatory diseases?J Neuroimmunol. 2005;166:3–18.

    Article  CAS  PubMed  Google Scholar 

  12. Ralevic V, Kendall DA, Randall MD, Smart D. Cannabinoid modulation of sensory neurotransmission via cannabinoid and vanilloid receptors: roles in regulation of cardiovascular function.Life Sci. 2002;71:2577–2594.

    Article  CAS  PubMed  Google Scholar 

  13. Crawley JN, Corwin RL, Robinson JK, Felder CC, Devane WA, Axelrod J. Anandamide, an endogenous ligand of the cannabinoid receptor, induces hypomotility and hypothermia in vivo in rodents.Pharmacol Biochem Behav. 1993;46:967–972.

    Article  CAS  PubMed  Google Scholar 

  14. Ross RA. Anandamide and vanilloid TRPV1 receptors.Br J Pharmacol. 2003;140:790–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hanus L, Gopher A, Almog S, Mechoulam R. Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor.J Med Chem. 1993;36:3032–3034.

    Article  CAS  PubMed  Google Scholar 

  16. Kuehl FA, Jr, Jacob TA, Ganley OH, Ormond RE, Meisinger MAP. The identification of N-2 (hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent.J Am Chem Soc. 1957;79:5577–5578.

    Article  CAS  Google Scholar 

  17. Bachur NR, Masek K, Melmon KL, Udenfriend S. Fatty acid amides of ethanolamine in mammalian tissues.J Biol Chem. 1965;240:1019–1024.

    CAS  PubMed  Google Scholar 

  18. Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids.Nature. 1998;394:277–281.

    Article  CAS  PubMed  Google Scholar 

  19. Fontana A, Di Marzo V, Cadas H, Piomelli D. Analysis of anandamide, an endogenous cannabinoid substance, and of other natural N-acylethanolamines.Prostaglandins Leukot Essent Fatty Acids. 1995;53:301–308.

    Article  CAS  PubMed  Google Scholar 

  20. Fu J, Gaetani S, Oveisi F, et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha.Nature. 2003;425:90–93.

    Article  CAS  PubMed  Google Scholar 

  21. Guzman M, Lo Verme J, Fu J, Oveisi F, Blazquez C, Piomelli D. Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-alpha).J Biol Chem. 2004;279:27849–27854.

    Article  CAS  PubMed  Google Scholar 

  22. Ahern GP. Activation of TRPV1 by the satiety factor oleoylethanolamide.J Biol Chem. 2003;278:30429–30434.

    Article  CAS  PubMed  Google Scholar 

  23. Chu CJ, Huang SM, De Petrocellis L, et al. N-oleoldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia.J Biol Chem. 2003;278:13633–13639.

    Article  CAS  PubMed  Google Scholar 

  24. De Petrocellis L, Chu CJ, Moriello AS, Kellner JC, Walker JM, Marzo VD. Actions of two naturally occurring saturated N-acyldopamines on transient receptor potential vanilloid 1 (TRPV1) channels.Br J Pharmacol. 2004;143:251–256.

    Article  PubMed  Google Scholar 

  25. Sheskin T, Hanus L, Slager J, Vogel Z, Mechoulam R. Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor.J Med Chem. 1997;40:659–667.

    Article  CAS  PubMed  Google Scholar 

  26. Milman G, Maor Y, Abu-Lafi S, et al. N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties.Proc Natl Acad Sci USA. 2006;103:2428–2433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hansen HS, Lauritzen L, Moesgaard B, Strand AM, Hansen HH. Formation of N-acyl-phosphatidylethanolamines and N-acetylethanolamines: proposed role in neurotoxicity.Biochem Pharmacol. 1998;55:719–725.

    Article  CAS  PubMed  Google Scholar 

  28. Josephs JL. Detection and characterization of fumonisin mycotoxins by liquid chromatography/electrospray ionization using ion trap and triple quadrupole mass spectrometry.Rapid Commun Mass Spectrom. 1996;10:1333–1344.

    Article  CAS  PubMed  Google Scholar 

  29. Scholz K, Dekant W, Volkel W, Pahler A. Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer.J Am Soc Mass Spectrom. 2005;16:1976–1984.

    Article  CAS  PubMed  Google Scholar 

  30. Schwudke D, Oegema J, Burton L, et al. Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition.Anal Chem. 2006;78:585–595.

    Article  CAS  PubMed  Google Scholar 

  31. Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF. Assignment of endogenous substrates to enzymes by global metabolite profiling.Biochemistry. 2004;43:14332–14339.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Michael Walker.

Additional information

Published: July 14, 2006

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, B., Bradshaw, H.B., Rimmerman, N. et al. Targeted lipidomics: Discovery of new fatty acyl amides. AAPS J 8, 54 (2006). https://doi.org/10.1208/aapsj080354

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/aapsj080354

Keywords

Navigation