Kalsner S
Br J Pharmacol. 1981 Jun;73(2):363-71. doi: 10.1111/j.1476-5381.1981.tb10430.x.
1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic alpha-adrenoceptors was investigated in guinea-pig atria previously incubated with [(3)H]-noradrenaline.2 Atria were stimulated with 100 pulses at various frequencies (1 to 15 Hz) in standard (2.3 mm), low (0.26 mm) and high (6.9 mm) calcium-Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine.3 The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium-Krebs solutions respectively.4 Noradrenaline inhibited the overflow of tritium in low calcium-Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium-Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium-Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium-Krebs solution. The patterns of inhibition and enhancement of stimulation-induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations.5 It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of release by transmitter is exceedingly unlikely under ordinary conditions of neurotransmission.
在预先用[³H] - 去甲肾上腺素孵育的豚鼠心房中，研究了钙离子流入神经末梢与突触前肾上腺素能受体功能的关系，以及由于神经元内钙积累导致的脱敏作用可能掩盖肾上腺素能受体激动剂和拮抗剂对突触前α - 肾上腺素能受体的影响。
在无药物存在时，以及先加入去甲肾上腺素随后加入酚苄明的情况下，分别在标准（2.3 mmol/L）、低（0.26 mmol/L）和高（6.9 mmol/L）钙 - 克雷布斯溶液中，以不同频率（1至15 Hz）对心房进行100次脉冲刺激。
每脉冲的氚溢出量与克雷布斯溶液中的钙浓度直接相关，在0.26 mmol/L和6.9 mmol/L钙 - 克雷布斯溶液中分别大幅降低和显著增加。
去甲肾上腺素在低钙 - 克雷布斯溶液中抑制氚的溢出，在一定程度上相对恒定，与频率无关。此外，该激动剂在标准钙 - 克雷布斯溶液中的最大抑制作用比在低钙溶液中更大。在高钙 - 克雷布斯溶液中，该儿茶酚胺在最低和最高频率下对溢出的抑制效果与在标准钙 - 克雷布斯溶液中一样有效。酚苄明总是增加氚的溢出，但在低钙和高钙 - 克雷布斯溶液中通常效果较差。这两种药物对刺激诱导的氚溢出的抑制和增强模式并未表明钙内流与肾上腺素能受体激活之间存在密切关系；脱敏似乎也不足以解释在三种不同钙浓度下刺激频率与激动剂和拮抗剂效应强度之间的关系。
得出的结论是，肾上腺素能递质的神经周水平并不能决定外源性肾上腺素能受体激动剂和拮抗剂对氚溢出的作用大小，并且在神经传递的正常条件下，递质对释放的负反馈调节极不可能。
