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.
Garcia
M C
MC
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
Kim
H Y
HY
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine