Chemical synthesis, pharmacological characterization, and possible formation in unicellular fungi of 3-hydroxy-anandamide

L. De Petrocellis, R. Deva, F. Mainieri, M. Schaefer, T. Bisogno, R. Ciccoli, A. Ligresti, K. Hill, S. Nigam, G. Appendino, V. Di Marzo

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Abstract

The fungal pathogen Candida albicans transforms arachidonic acid (AA) into 3-hydroxyarachidonic acid [3(R)-HETE], and we investigated if its nonpathogenic and 3(R)-HETE-producing close relative, Dipodascopsis uninucleata, could similarly transform the endocannabinoid/endovanilloid anandamide into 3-hydroxyanandamide (3-HAEA). We found that D. uninucleata converts anandamide into 3-HAEA, and we therefore developed an enantiodivergent synthesis for this compound to study its pharmacological activity. Both enantiomers of 3-HAEA were as active as anandamide at elevating intracellular Ca2+via TRPV1 receptors overexpressed in HEK-293 cells, while a∼70-90-fold and ∼45-60-fold lower affinity at cannabinoid CB1and CB2receptors was instead observed. Patch clamp recordings showed that 3(R)-HAEA activates a TRPV1-like current in TRPV1-expressing HEK-293 cells. Thus, 3(R)-HETE-producing yeasts might convert anandamide released by host cells at the site of infection into 3(R)-HAEA, and this eventmight contribute to the inflammatory and algogenous responses associated to fungal diseases. Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)658 - 666
Number of pages9
JournalJournal of Lipid Research
Volume50
Issue number4
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

De Petrocellis, L., Deva, R., Mainieri, F., Schaefer, M., Bisogno, T., Ciccoli, R., ... Di Marzo, V. (2009). Chemical synthesis, pharmacological characterization, and possible formation in unicellular fungi of 3-hydroxy-anandamide. Journal of Lipid Research, 50(4), 658 - 666. https://doi.org/10.1194/jlr.M800337-JLR200