Msghina M, Mermet C, Gonon F, Stjärne L
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):173-86. doi: 10.1007/BF00165299.
The aim of this study was to investigate whether or not nerve impulses release ATP and noradrenaline in parallel from the sympathetic nerve terminals of the rat tail artery. The extracellularly recorded excitatory junction current (EJC) was used to study, pulse by pulse, the release of ATP. An electrochemical method was used to study online the nerve stimulation-induced rise in the extracellular concentration of endogenous noradrenaline at the probe, a carbon fibre electrode (CF). This parameter, which does not directly represent noradrenaline release, but reflects release minus clearance, has been termed delta[NA]CF. The effects of a number of pharmacological agents on the EJCs were examined both at 0.1 and 2 Hz, and the effects on the EJC response to 100 pulses at 2 Hz compared with that on the delta[NA]CF response. Clonidine and xylazine were used as alpha 2-agonists, yohimbine and idazoxan as alpha 2-antagonists and desipramine and cocaine as blockers of noradrenaline reuptake. Most of these agents had unwanted side effects, especially at higher concentrations. However, clonidine and xylazine depressed at lower concentrations the EJC and delta[NA]CF responses to about the same extent; these effects were partially or completely reversed by yohimbine. Yohimbine or idazoxan did not affect the EJCs at 0.1 Hz but enhanced the EJC and delta[NA]CF responses to 100 pulses at 2 Hz to the same extent. All effects of desipramine (1 microM) seemed explainable as a result of block of noradrenaline reuptake, while cocaine (10 microM) in addition exerted an 'unspecific' depressant (probably local anesthetic) effect. Under control conditions, both agents depressed the EJC but dramatically enhanced the delta[NA]CF response to 100 pulses at 2 Hz. Addition of yohimbine prevented the depressant effect of desipramine on the EJCs completely and reduced that of cocaine, but increased their effects on the delta[NA]CF response. These results are compatible with the view that ATP and noradrenaline are released in parallel from the sympathetic nerve terminals of this tissue. The different, and under some conditions even opposite, effects of desipramine or cocaine on the EJC and delta[NA]CF responses are explainable in terms of the known post-secretory effects of these agents.
本研究的目的是调查大鼠尾动脉交感神经末梢的神经冲动是否会同时释放ATP和去甲肾上腺素。细胞外记录的兴奋性接头电流（EJC）用于逐脉冲研究ATP的释放。采用电化学方法在线研究神经刺激引起的探针（碳纤维电极，CF）处内源性去甲肾上腺素细胞外浓度的升高。这个参数并不直接代表去甲肾上腺素的释放，而是反映释放量减去清除量，被称为δ[NA]CF。在0.1和2Hz频率下，研究了多种药理剂对EJC的影响，并将其对2Hz频率下100个脉冲的EJC反应的影响与对δ[NA]CF反应的影响进行了比较。可乐定和赛拉嗪用作α2激动剂，育亨宾和咪唑克生用作α2拮抗剂，地昔帕明和可卡因用作去甲肾上腺素再摄取阻滞剂。这些药剂中的大多数都有不良副作用，尤其是在较高浓度时。然而，可乐定和赛拉嗪在较低浓度下对EJC和δ[NA]CF反应的抑制程度大致相同；育亨宾可部分或完全逆转这些作用。育亨宾或咪唑克生在0.1Hz频率下不影响EJC，但在2Hz频率下对100个脉冲的EJC和δ[NA]CF反应的增强程度相同。地昔帕明（1μM）的所有作用似乎都可以解释为去甲肾上腺素再摄取受阻的结果，而可卡因（10μM）除了产生“非特异性”抑制作用（可能是局部麻醉作用）外，还会产生这种作用。在对照条件下，这两种药剂都会抑制EJC，但会显著增强2Hz频率下100个脉冲的δ[NA]CF反应。加入育亨宾可完全防止地昔帕明对EJC的抑制作用，并降低可卡因的抑制作用，但会增加它们对δ[NA]CF反应的作用。这些结果与ATP和去甲肾上腺素从该组织的交感神经末梢同时释放的观点一致。地昔帕明或可卡因对EJC和δ[NA]CF反应的不同，甚至在某些情况下相反的作用，可以根据这些药剂已知的分泌后作用来解释。
