Mobilization of arachidonate and docosahexaenoate by stimulation of the 5-HT2A receptor in rat C6 glioma cells.

In this study, we demonstrate that astroglial 5-HT2A receptors are linked to the mobilization of polyunsaturated fatty acids (PUFA). Stimulation of C6 glioma cells, prelabeled with [3H]arachidonate (AA, 20:4n6) and [14C]docosahexaenoate (DHA, 22:6n3), with serotonin and the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) resulted in the mobilization of both [3H] and [14C] into the supernatant of the cell monolayers. The increased radioactivity in the supernatant was mainly associated with free fatty acids. Experiments using inhibitors of phosphoinositide-specific phospholipase C and PLA2, inhibited the DOI-stimulated mobilization of AA and DHA, suggesting the involvement of both phospholipases. Ketanserin (1 microM), a 5-HT(2A/2C) receptor antagonist, and MDL 100,907 (R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-pi peridine-methanol) (1 microM), a highly selective antagonist for 5-HT2A receptors, significantly decreased the DOI-stimulated release of AA and DHA. These results indicate that the 5-HT2A receptor is coupled to the mobilization of PUFA. The release of AA and DHA in response to serotonin may represent a mechanism through which astroglia provide these polyunsaturated fatty acids to neurons.