Garcia M C, Kim H Y
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
Brain Res. 1997 Sep 12;768(1-2):43-8. doi: 10.1016/s0006-8993(97)00583-0.
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.
在本研究中，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[3H]花生四烯酸（AA，20:4n6）和[14C]二十二碳六烯酸（DHA，22:6n3）预标记的C6胶质瘤细胞，用血清素和5-HT(2A/2C)受体激动剂（±）-2,5-二甲氧基-4-碘苯丙胺盐酸盐（DOI）刺激后，[3H]和[14C]均被动员到细胞单层的上清液中。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PLA2抑制剂的实验，抑制了DOI刺激的AA和DHA的动员，提示两种磷脂酶均参与其中。5-HT(2A/2C)受体拮抗剂酮色林（1 microM）和5-HT2A受体的高度选择性拮抗剂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 microM），显著降低了DOI刺激的AA和DHA的释放。这些结果表明5-HT2A受体与PUFA的动员有关。响应血清素释放的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一种机制。
