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Serotonin 5‐HT 2A receptor activation induces 2‐arachidonoylglycerol release through a phospholipase c‐dependent mechanism
Author(s) -
Parrish Jason C.,
Nichols David E.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04173.x
Subject(s) - 2 arachidonoylglycerol , endocannabinoid system , phospholipase c , receptor , chemistry , 5 ht receptor , phospholipase d , phospholipase , phospholipase a2 , serotonin , cannabinoid receptor , biology , biochemistry , signal transduction , enzyme , agonist
To date, several studies have demonstrated that phospholipase C‐coupled receptors stimulate the production of endocannabinoids, particularly 2‐arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C‐coupled serotonin 5‐HT 2A receptor‐mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation of the 5‐HT 2A receptor leads to the production and release of the endocannabinoid 2‐arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5‐HT 2A receptor were first incubated with [ 3 H]‐arachidonic acid for 24 h. Following stimulation with 10 μ m serotonin, lipids were extracted from the assay medium, separated by thin layer chromatography, and analyzed by liquid scintillation counting. Our results indicate that 5‐HT 2A receptor activation stimulates the formation and release of 2‐arachidonoylglycerol. The 5‐HT 2A receptor‐dependent release of 2‐arachidonoylglycerol was partially dependent on phosphatidylinositol‐specific phospholipase C activation. Diacylglycerol produced downstream of 5‐HT 2A receptor‐mediated phospholipase D or phosphatidylcholine‐specific phospholipase C activation did not appear to contribute to 2‐arachidonoylglycerol formation in NIH3T3–5HT 2A cells. In conclusion, our results support a functional model where neuromodulatory neurotransmitters such as serotonin may act as regulators of endocannabinoid tone at excitatory synapses through the activation of phospholipase C‐coupled G‐protein coupled receptors.