Callado L F, Stamford J A
Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, St. Bartholomew's and Royal London School of Medicine and Dentistry, Royal London Hospital, London, England.
J Neurochem. 2000 Jun;74(6):2350-8. doi: 10.1046/j.1471-4159.2000.0742350.x.
We investigated the roles of alpha(2) autoreceptors and noradrenaline (NA) transporters on NA efflux and uptake in the rat locus coeruleus after electrical stimulation. NA efflux was evoked by various trains (50 pulses, 10-500 Hz) and measured by fast cyclic voltammetry. NA efflux and uptake half-time (t(1/2)) were stimulus-dependent, ranging from 43 +/- 3 nM and 2.45 +/- 0.21 s, respectively, with 500-Hz stimuli to 127 +/- 11 nM and 4.41 +/- 0.34 s, respectively, with 100-Hz trains. Based on these data, we calculate that each transporter removes 0.19 NA molecules from the extracellular space every second, a velocity compatible more with transporter-than channel-mode conduction. Dexmedetomidine (10 nM) decreased NA efflux by approximately 30% on stimulations of < or =1 s in duration. BRL 44408 (1 microM) increased NA efflux on stimuli of > or =2 s (by up to 92 +/- 16%). Desipramine (50 nM) increased NA efflux on stimuli of > or =1 s (by 113 +/- 24%) but slowed NA uptake on all stimuli. When given together, the effects of desipramine and BRL 44408 were additive at stimuli of >or =1 s but showed potentiation on shorter trains. There was a significant time delay for the elevation of NA efflux by blockade of uptake (0.79 s) or autoreceptors (1.14 s), suggesting that both are located extrasynaptically and that NA must diffuse through the extracellular space to these structures. We suggest that released NA may interact with alpha(2) autoreceptors and NA transporters as far as 10 microm from the release sites, an action compatible with a volume transmission role of NA in the locus coeruleus.
我们研究了α₂ 自身受体和去甲肾上腺素（NA）转运体在电刺激后大鼠蓝斑中NA外流和摄取过程中的作用。通过不同的刺激序列（50个脉冲，10 - 500 Hz）诱发NA外流，并采用快速循环伏安法进行测量。NA外流和摄取的半衰期（t₁/₂）依赖于刺激，500 Hz刺激时分别为43±3 nM和2.45±0.21 s，100 Hz序列刺激时分别为127±11 nM和4.41±0.34 s。基于这些数据，我们计算出每个转运体每秒从细胞外空间移除0.19个NA分子，该速度更符合转运体而非通道模式传导。右美托咪定（10 nM）在持续时间≤1 s的刺激下使NA外流减少约30%。BRL 44408（1 μM）在持续时间≥2 s的刺激下使NA外流增加（增加高达92±16%）。地昔帕明（50 nM）在持续时间≥1 s的刺激下使NA外流增加（增加113±24%），但在所有刺激下均减慢NA摄取。当联合使用时，地昔帕明和BRL 44408在持续时间≥1 s的刺激下作用相加，但在较短刺激序列时表现出增强作用。通过阻断摄取（0.79 s）或自身受体（1.14 s）来升高NA外流存在显著的时间延迟，这表明两者均位于突触外，并且NA必须通过细胞外空间扩散至这些结构。我们认为，释放的NA可能与距离释放位点达10微米远的α₂ 自身受体和NA转运体相互作用，这一作用符合NA在蓝斑中的容积传递作用。
