Silva Juliara Henriques, Gomez Marcus Vinicius, Silva Janice Henriques, Guatimosim Cristina, Gomez Renato Santiago
Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Neurochem Int. 2008 May;52(6):1240-6. doi: 10.1016/j.neuint.2008.01.004. Epub 2008 Jan 12.
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 [3H]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 [3H]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 halothane-evoked [3H]5-HT release was reduced by BAPTA-AM, a membrane-permeable BAPTA analog that chelates intracellular Ca2+. The anesthetic-induced [3H]5-HT release depends on the ryanodine-sensitive 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 [3H]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 [3H]5-HT release is reduced by fluoxetine, an inhibitor of 5-HT uptake, and the volatile agent also decreased the uptake of [3H]5-HT into rat brain cortical slices. Moreover, a decrease on halothane-induced release of [3H]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 [3H]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 [3H]5-HT in rat brain cortical slices.
血清素能系统可能在全身麻醉过程中发挥作用，但挥发性麻醉剂氟烷对血清素（5-羟色胺，5-HT）释放的影响尚未完全明确。用[3H]5-HT标记大鼠脑皮质切片，以研究氟烷对这种神经递质从中枢神经系统释放的影响。氟烷引起[3H]5-HT释放增加，这取决于孵育时间和麻醉剂浓度（0.006、0.012、0.024、0.036、0.048和0.072 mM）。这种效应与细胞外钙无关，且不受河豚毒素（电压依赖性Na+通道阻滞剂）的影响。相反，膜通透性BAPTA类似物BAPTA-AM（可螯合细胞内Ca2+）可减少氟烷诱发的[3H]5-HT释放。麻醉诱导的[3H]5-HT释放依赖于对兰尼碱敏感的细胞内钙库，因为它被丹曲林和阿祖莫林（通过兰尼碱受体释放钙的抑制剂）阻断，但不受1,4,5-三磷酸肌醇受体抑制剂2-氨基乙氧基二苯硼酸（2-APB）的影响。氟烷诱导的[3H]5-HT释放主要来自囊泡池，因为利血平（一种囊泡单胺转运体阻滞剂）可使其释放减少约70%。5-羟色胺摄取抑制剂氟西汀可减少氟烷诱发的[3H]5-HT释放，且该挥发性药物还降低了[3H]5-HT进入大鼠脑皮质切片的摄取。此外，当脑皮质切片在低温下孵育时，也观察到氟烷诱导的[3H]5-HT释放减少，已知低温会干扰神经递质的载体介导释放。Na+/K+ ATP酶泵抑制剂哇巴因通过逆向转运诱导5-羟色胺释放，它也减少了氟烷诱导的[3H]5-HT释放，证实了在氟烷存在下神经递质的载体介导释放参与其中。总之，这些数据表明氟烷在大鼠脑皮质切片中诱导囊泡和载体介导的[3H]5-HT释放。
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