Valtonen P, Haapalinna A, Riekkinen P, Halonen T
A.I. Virtanen Institute, University of Kuopio, Finland.
Eur J Pharmacol. 1995 Oct 24;285(3):239-46. doi: 10.1016/0014-2999(95)00405-a.
alpha 2-Adrenoceptors are known to be involved in a variety of physiological functions and pathological conditions, including epilepsy and the extent of excitotoxin-induced cell death. In this study we evaluated whether selective alpha 2-adrenergic drugs can modulate the release of neurotransmitter amino acids. The effect of the alpha 2-adrenoceptor agonist dexmedetomidine (5 micrograms/kg, s.c.) and the alpha 2-adrenoceptor antagonist atipamezole (0.1 mg/kg and 1 mg/kg, s.c.) on the release of extracellular glutamate, aspartate and gamma-aminobutyric acid (GABA) was studied with microdialysis in the hippocampus of freely moving rats under basal and K(+)-evoked conditions. Atipamezole (1 mg/kg) decreased K(+)-evoked glutamate efflux by 30% compared to the control group (P < 0.05) but did not affect significantly the effluxes of aspartate and GABA. Dexmedetomidine and the lower dose of atipamezole (0.1 mg/kg) did not significantly alter the evoked overflow of amino acids. The results suggest that alpha 2-adrenergic drugs have only modest effects on the K(+)-stimulated overflow of extracellular neurotransmitter amino acids in rat hippocampus.
已知α2 - 肾上腺素能受体参与多种生理功能和病理状况,包括癫痫以及兴奋性毒素诱导的细胞死亡程度。在本研究中,我们评估了选择性α2 - 肾上腺素能药物是否能调节神经递质氨基酸的释放。采用微透析技术,在自由活动大鼠的海马体中,研究了α2 - 肾上腺素能受体激动剂右美托咪定(5微克/千克,皮下注射)和α2 - 肾上腺素能受体拮抗剂阿替美唑(0.1毫克/千克和1毫克/千克,皮下注射)在基础状态和钾离子诱发条件下对细胞外谷氨酸、天冬氨酸和γ - 氨基丁酸(GABA)释放的影响。与对照组相比,阿替美唑(1毫克/千克)使钾离子诱发的谷氨酸流出量减少了30%(P < 0.05),但对天冬氨酸和GABA的流出量没有显著影响。右美托咪定和较低剂量的阿替美唑(0.1毫克/千克)并未显著改变诱发的氨基酸溢出。结果表明,α2 - 肾上腺素能药物对大鼠海马体中钾离子刺激的细胞外神经递质氨基酸溢出仅有适度影响。