Enero M A
Naunyn Schmiedebergs Arch Pharmacol. 1984 Nov;328(1):38-40. doi: 10.1007/BF00496103.
Conditions required for the inhibitory feedback modulation of noradrenergic neurotransmission were studied in isolated atria of the rat. The alpha adrenergic antagonist, yohimbine, 0.8 microM, or phentolamine, 1 microM, did not affect the chronotropic response to 4 or 8 shocks at 0.8 Hz but increased it when a higher number of shocks was applied. When neuronal uptake was inhibited by cocaine, 2.9 microM, or desipramine, 0.1 microM, the enhancement of neurotransmission by yohimbine or phentolamine was higher than that observed in the presence of alpha-adrenergic antagonists alone. In atria preincubated with 3H-noradrenaline, the effect of the drugs on the 3H-overflow evoked by 240 shocks at 2.0 Hz was studied. Cocaine 2.9 microM, did not increase the evoked overflow but yohimbine, 0.8 microM, did. The 3H-overflow obtained in the group of yohimbine plus cocaine was significantly higher than was expected from the effects of both drugs alone. It is concluded that yohimbine or phentolamine enhance the chronotropic response in rat atria only when the concentration of noradrenaline in the biophase is sufficiently high to activate presynaptic receptors. In this tissue, the efficiency of the neuronal uptake influences the degree of alpha-adrenergic autoinhibition.
在大鼠离体心房中研究了去甲肾上腺素能神经传递抑制性反馈调节所需的条件。0.8微摩尔的α肾上腺素能拮抗剂育亨宾或1微摩尔的酚妥拉明，对0.8赫兹下4次或8次电击的变时反应没有影响，但在施加更多次数电击时会增强该反应。当神经元摄取被2.9微摩尔的可卡因或0.1微摩尔的地昔帕明抑制时，育亨宾或酚妥拉明对神经传递的增强作用高于单独使用α肾上腺素能拮抗剂时观察到的效果。在用3H-去甲肾上腺素预孵育的心房中，研究了药物对2.0赫兹下240次电击诱发的3H溢出的影响。2.9微摩尔的可卡因没有增加诱发的溢出，但0.8微摩尔的育亨宾增加了。育亨宾加可卡因组获得的3H溢出显著高于两种药物单独作用的预期值。结论是，只有当生物相中去甲肾上腺素的浓度足够高以激活突触前受体时，育亨宾或酚妥拉明才会增强大鼠心房的变时反应。在该组织中，神经元摄取的效率影响α肾上腺素能自身抑制的程度。
