Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Adv Exp Med Biol. 2017;975 Pt 2:1129-1140. doi: 10.1007/978-94-024-1079-2_90.
Fluoxetine, an antidepressant and selective serotonin reuptake inhibitor, modulates immune cells in vitro. The present study investigates the influence of pharmacological agents which acts as agonist and antagonist of serotonin receptors ex vivo over taurine transport in lymphocytes of rats treated with fluoxetine by one week. The treatment with fluoxetine increase taurine transport and the incubation with the agonist of 5-HT receptor, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) counteract this effect, and ketanserin provoked no change in fluoxetine effect. While the agonist of 5-HT receptor, 4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphth alenyl)-1-piperazinehexanamide hydrochloride (LP44) had no significant effects, however the differences between Control and Fluoxetine groups were not observed, the antagonist (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no differences. Preincubation of cells with the diacylglycerol analogue, 1-oleoyl-2-acetyl-sn-glycerol (OAG) caused inhibition of fluoxetine treatment effect but this not occurred in presence of the PKC inhibitor, 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG-C). Forskolin counteracted the effect of fluoxetine on taurine transport, since at the concentrations used, the rate of taurine transport in Fluoxetine group, returned to Control rate. No significant differences were observed with the PKA inhibitor. Although it is not possible to attribute a definitive role of 5-HT receptors in fluoxetine effect on taurine transport, its signaling might affect the function of it. Participation of PKC and PKA have an apparently relevant role in lymphocyte taurine transport.
氟西汀是一种抗抑郁药和选择性 5-羟色胺再摄取抑制剂,可在体外调节免疫细胞。本研究探讨了作为 5-羟色胺受体激动剂和拮抗剂的药物在体外对经过一周氟西汀处理的大鼠淋巴细胞中牛磺酸转运的影响。氟西汀治疗增加了牛磺酸的转运,而 5-羟色胺受体激动剂 1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)的孵育则抵消了这种作用,酮色林对氟西汀作用无影响。虽然 5-羟色胺受体激动剂 4-[2-(甲硫基)苯基]-N-(1,2,3,4-四氢-1-萘基)-1-哌嗪己烷甲酰胺盐酸盐(LP44)没有显著作用,但在对照组和氟西汀组之间没有观察到差异,拮抗剂 (R)-3-[2-[2-(4-甲基哌啶-1-基)乙基]吡咯烷-1-磺酰基]苯酚盐酸盐(SB269970)也没有差异。细胞与二酰基甘油类似物 1-油酰基-2-乙酰基-sn-甘油(OAG)孵育可抑制氟西汀治疗效果,但在蛋白激酶 C 抑制剂 1-O-十六烷基-2-O-甲基-rac-甘油(AMG-C)存在下则不会发生。forskolin 可拮抗氟西汀对牛磺酸转运的作用,因为在所用浓度下,氟西汀组的牛磺酸转运率恢复到对照率。PKA 抑制剂无显著差异。虽然不能明确 5-羟色胺受体在氟西汀对牛磺酸转运的作用中起决定性作用,但它的信号可能会影响其功能。PKC 和 PKA 的参与在淋巴细胞牛磺酸转运中显然具有重要作用。