Mobilization of arachidonate and docosahexaenoate by stimulation of the 5-HT2A receptor in rat C6 glioma cells
Mobilization of arachidonate and docosahexaenoate by stimulation of the 5-HT2A receptor in rat C6 glioma cells
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DOI：
10.1016/s0006-8993(97)00583-0
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发表时间：
1997-09-12
期刊：
影响因子：
2.9
通讯作者：
Kim, HY
中科院分区：
文献类型：
--
作者：
Garcia, MC;Kim, HY
在这项研究中，我们证明星形胶质细胞 5-HT2A 受体与多不饱和脂肪酸 (PUFA) 的动员有关。用 [(3)Hlarachidonate (AA, 20:4n6) 和 [C-14]二十二碳六烯酸 (DHA, 22:6n3) 预标记的 C6 神经胶质瘤细胞，用血清素和 5-HT2A/2C 受体激动剂 (+/-)-2,5-dimethoxy-4-iodoamphetamine 盐酸盐 (DOI) 进行刺激 导致[H-3]和[C-14]动员到单层细胞的上清液中。上清液中放射性的增加主要与游离脂肪酸有关。使用磷酸肌醇特异性磷脂酶 C 和 PLA(2) 抑制剂的实验抑制了 DOI 刺激的 AA 和 DHA 动员，表明两种磷脂酶都参与其中。 5-HT2A/2C 受体拮抗剂 Ketanserin (1 μM) 和 5-HT2A 受体高选择性拮抗剂 MDL 100,907 (R(+)-α-(2,3-二甲氧基苯基)]-1-[2-(4-氟苯基乙基)]-4-哌啶-甲醇) (1 μM) 显着降低了 DOI 刺激 AA 和 DHA 的释放。这些结果表明 5-HT2A 受体与 PUFA 的动员相关。响应血清素而释放 AA 和 DHA 可能代表星形胶质细胞向神经元提供这些多不饱和脂肪酸的机制。 (C) 1997 Elsevier Science B.V.
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 [(3)Hlarachidonate (AA, 20:4n6) and [C-14]docosahexaenoate (DHA, 22:6n3), with serotonin and the 5-HT2A/2C receptor agonist(+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) resulted in the mobilization of both [H-3] and [C-14] 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 PLA(2), inhibited the DOI-stimulated mobilization of AA and DHA, suggesting the involvement of both phospholipases. Ketanserin (1 mu M), a 5-HT2A/2C receptor antagonist, and MDL 100,907 (R(+)-alpha-(2,3-dimethoxyphenyl)]-1-[2-(4-fluophenylethyl)]-4-piperidine-methanol) (1 mu M), 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. (C) 1997 Elsevier Science B.V.