Halothane induces vesicular and carrier-mediated release of [3H]serotonin from rat brain cortical slices

被引:5
|
作者
Silva, Juliara Henriques [2 ]
Gornez, Marcus Vinicius [3 ]
Silva, Janice Henriques [2 ]
Guatimosim, Cristina [4 ]
Gomez, Renato Santiago [1 ]
机构
[1] Univ Fed Minas Gerais, Dept Cirurgia, Fac Med, Sch Med,Dept Surg, BR-30130100 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Pharmacol, Inst Biol Sci, BR-30130100 Belo Horizonte, MG, Brazil
[3] Nucl Posgrad Santa Casa, Belo Horizonte, MG, Brazil
[4] Univ Fed Minas Gerais, Inst Biol Sci, Dept Morphol, BR-30130100 Belo Horizonte, MG, Brazil
关键词
carrier-mediated release; halothane; rat brain cortical slices; serotonin; serotonin transporter; vesicular release;
D O I
10.1016/j.neuint.2008.01.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The serotonergic system may play a role during general anesthesia but the effect of the volatile anesthetic halothane on the release of serotonin (5-HT) is not fully understood. Rat brain cortical slices were labeled with [H-3]5-HT to investigate the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [H-3]5-HT that was dependent on incubation time and anesthetic concentration (0.006, 0.012, 0.024, 0.036, 0.048 and 0.072 mM). This effect was independent of extracellular calcium and was not affected by tetrodotoxin (blocker of voltage dependent Na+ channels). In contrast, the halotbane-evoked [H-3]5-HT release was reduced by BAPTA-AM, a membrane-permeable BAPTA analog that chelates intracellular Ca2+. The anesthetic-induced [H-3]5-HT release depends on the ryanodinesensitive intracellular calcium store since it was blocked by dantrolene and azumolene (inhibitors of the calcium-release through ryanodine receptors) but was not affected by aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-triphosphate receptor. The [H-3]5-HT release induced by halothane comes mainly from the vesicular pool since it was reduced in about 70% by reserpine, a blocker of vesicular monoamine transporter. The halothane-evoked release of [H-3]5-HT release is reduced by fluoxetine, an inhibitor of 5-HT uptake, and the volatile agent also decreased the uptake of [H-3]5-HT into rat brain cortical slices. Moreover, a decrease on halothane-induced release of [H-3]5-HT was also observed when the brain cortical slices were incubated at low temperature, which is known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na+/K+ ATPase pump inhibitor, which induces 5-HT release through reverse transport, also decreased [H-3]5-HT release induced by halothane, confirming the involvement of a carrier-mediated release of the neurotransmitter in the presence of halothane. In conclusion, these data suggest that halothane induces vesicular and carrier-mediated release of [H-3]5-HT in rat brain cortical slices. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1240 / 1246
页数:7
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