Stjärne L, Bao J X, Gonon F, Msghina M
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1994 Jun;60(4):1021-38. doi: 10.1016/0306-4522(94)90280-1.
The aim of this study was to find out if clearance of noradrenaline released from sympathetic nerve terminals in rat isolated tail artery is a physiological variable and if so, to determine its role for the noradrenaline-mediated neurogenic contraction. The per pulse release of noradrenaline induced by electrical nerve stimulation and the fluctuations of the level of noradrenaline at the receptors driving the contractions were assessed from the electrochemically determined noradrenaline oxidation current at a carbon fibre electrode at the surface of the artery. Both were compared with the noradrenaline-mediated neurogenic contraction. The effects on these parameters of cocaine or desipramine, or of corticosterone, were used to assess the relative roles of neuronal and extraneuronal uptake, respectively. The effects of cocaine or desipramine, which enhance the noradrenaline level at the receptors by blocking neuronal reuptake, were compared with those of yohimbine, presumed to act exclusively by enhancing the per pulse release of noradrenaline. The results seem to support the following tentative conclusions. Clearance of released noradrenaline occurs by neuronal uptake and diffusion, while extraneuronal uptake is negligible. The noradrenaline-induced neurogenic contraction is mediated via adrenoceptors on cells near the plane of the nerve plexus; the excitation spreads from these cells throughout the syncytium. The contractile response to exogenous noradrenaline may also be mediated via receptors on the innervated key cells. Reuptake of noradrenaline into the releasing varicosities, i.e. in "active junctions", is highly efficient for single quanta but rapidly saturated by repeated release, while reuptake of noradrenaline in the "surround" of active junctions is probably rarely saturated and more independent of nerve activity. Saturation of the transporter by repeated release of quanta from the same varicosity and the consequent accumulation of "residual" noradrenaline and increased diffusion out of the junction and recruitment of noradrenaline receptors in the surround may be the cause of the rapid growth of the contraction during a high frequency train. Diffusion of released noradrenaline away from the postjunctional receptors is restricted by a local nerve activity-dependent buffering mechanism which, in spite of fading of the per pulse release, helps maintain the noradrenaline concentration at the receptors and the contraction during long high-frequency trains. Reactivation of the clearance mechanisms upon cessation of nerve activity accelerates the relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是探究大鼠离体尾动脉中交感神经末梢释放的去甲肾上腺素的清除是否为一个生理变量，若如此，则确定其在去甲肾上腺素介导的神经源性收缩中的作用。通过在动脉表面的碳纤维电极上电化学测定去甲肾上腺素氧化电流，评估电刺激神经诱导的去甲肾上腺素的每脉冲释放量以及驱动收缩的受体处去甲肾上腺素水平的波动情况。将这两者与去甲肾上腺素介导的神经源性收缩进行比较。分别使用可卡因或地昔帕明、或皮质酮对这些参数的影响来评估神经元摄取和非神经元摄取的相对作用。将通过阻断神经元再摄取来提高受体处去甲肾上腺素水平的可卡因或地昔帕明的作用，与据推测仅通过增强去甲肾上腺素的每脉冲释放量起作用的育亨宾的作用进行比较。结果似乎支持以下初步结论。释放的去甲肾上腺素通过神经元摄取和扩散进行清除，而非神经元摄取可忽略不计。去甲肾上腺素诱导的神经源性收缩是通过神经丛平面附近细胞上的肾上腺素能受体介导的；兴奋从这些细胞传播到整个合体细胞。对外源性去甲肾上腺素的收缩反应也可能通过受神经支配的关键细胞上的受体介导。去甲肾上腺素重新摄取到释放曲张体中，即在“活性连接处”，对于单个量子来说效率很高，但会因重复释放而迅速饱和，而在活性连接处“周围”的去甲肾上腺素重新摄取可能很少饱和且更独立于神经活动。从同一曲张体重复释放量子导致转运体饱和，以及随之而来的“残余”去甲肾上腺素的积累、从连接处扩散增加以及周围肾上腺素能受体的募集，可能是高频串刺激期间收缩迅速增强的原因。释放的去甲肾上腺素从节后受体扩散出去受到局部神经活动依赖性缓冲机制的限制，尽管每脉冲释放量逐渐减弱，但该机制有助于在长时间高频串刺激期间维持受体处的去甲肾上腺素浓度和收缩。神经活动停止后清除机制的重新激活加速了舒张。（摘要截断于400字）
