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Activation of TRPC3 promotes endocannabinoid synthesis
Author(s) -
Bardell Tamera Kay,
Barker Eric L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1177-c
Subject(s) - trpc3 , endocannabinoid system , trpc , transient receptor potential channel , diacylglycerol lipase , microbiology and biotechnology , chemistry , anandamide , trpc5 , lipid raft , caveolae , 2 arachidonoylglycerol , arachidonic acid , biochemistry , cannabinoid receptor , biology , signal transduction , receptor , monoacylglycerol lipase , enzyme , agonist
Transient receptor potential (TRP) channels are calcium‐permeable channels. Canonical TRP (TRPC) channels are a homology‐based subdivision of the broader class of TRP channels. TRPC3 is a G‐protein‐gated nonselective cation channel that has been localized to lipid rafts and shown to colocalize with caveolin 1. Our lab has shown that a subset of lipid rafts rich in cholesterol and sphingolipids known as caveolae are involved in many endocannabinoid processes. The process of endocannabinoid synthesis and release is still unknown. Endocannabinoid synthesis has been found to occur on demand in a calcium‐dependent manner. Recently, we have verified the presence of TRPC3 in caveolae, suggesting a possible role for TRPC3 in endocannabinoid synthesis. Using lipid extraction and TLC analysis, we found that CAD cells pretreated with radiolabeled anandamide (AEA) produced a significant amount of AEA upon stimulation of TRPC3. Furthermore, cells pretreated with radiolabeled arachidonic acid exhibited a robust increase in 2‐arachidonylglycerol release in response to TRPC3 stimulation. We have also demonstrated that both the inhibition of TRPC3 and disruption of caveolae block endocannabinoid synthesis. This evidence suggests that TRPC3 plays a role in endocannabinoid synthesis and that this process is likely taking place within lipid raft microdomains. This research supported by grant R21 DA018112 from NIH