Effects of chronic ethanol on the mobilization of arachidonate and docosahexaenoate stimulated by the type 2A serotonin receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in C6 glioma cells.
We studied the effects of chronic ethanol exposure on the mobilization of polyunsaturated fatty acids stimulated by activation of the type 2A serotonin receptor in C6 glioma cells. In our in vitro model, we prelabeled cells with [3H]arachidonate and [14C]docosahexaenonate and subsequently stimulated with the type 2A serotonin receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride. In as early as 10 days of exposure to 20 or 50 mM ethanol, the (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-simulated mobilization of [3H]arachidonic acid [[3H]AA) and [14C]docosahexaenoic acid ([14C]DHA) was significantly inhibited, and this inhibition was accompanied by decreased mobilization of intracellular [Ca2+]i. Exposure to ethanol did not alter significantly the release of [3H]AA and [14C]DHA stimulated by the calcium ionophore A23187 nor the incorporation of [3H]AA and [14C]DHA into cellular lipids. Decreased mobilization of polyunsaturated fatty acids and calcium in astroglia may contribute to neurotoxicity caused by chronic ethanol exposure.
Garcia
M C
MC
Section of Mass Spectrometry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852. USA.
Kim
K Y
KY
Hough
C
C
Kim
H Y
HY
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects*; D001932:Brain Neoplasms; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005910:Glioma; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D000431:Ethanol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine