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标题：Chemical synthesis, pharmacological characterization, and possible formation in unicellular fungi of 3-hydroxy-anandamide
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作者：L. De Petrocellis ; R. Deva ; F. Mainieri 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：4
页码：658-666
DOI：10.1194/jlr.M800337-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 CB₁ and CB₂ receptors 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 event might contribute to the inflammatory and algogenous responses associated to fungal diseases.