Cubeddu L, Weiner N
J Pharmacol Exp Ther. 1975 Jan;192(1):1-14.
A frequency-dependent increase in the overflow of norepinephrine (NE), 3-H-NE, total 3-H and dopamine-beta-hydroxylase (DBH) activity per nerve impulse was obtained after electrical stimulation of the isolated, perfused cat spleen. Over the range of frequencies studied, a proportional increase in the overflow of transmitter and DBH activity was observed, suggesting that an increase in the exocytotic release of NE is the primary mechanism by which the overflow of transmitter is enhanced with increasing frequencies of stimulation. The effects of 3 muM phenoxybenzamine (PBA) on the nerve stimulation-mediated overflow of NE, total 3-h, 3-h-ne and DBH activity were studied at two frequencies of stimulation, 1 and 5 Hz, in spleens from control and alpha-methyl-p-tyrosine-treated cats. Similarly, release of DBH activity was studied in spleens of reserpine-treated cats. In spleens from control cats, PBA produced a marked increase in the overflow of transmitter and DBH activity. This enhancement was more pronounced at 5 Hz than at 1 Hz. It was estimated that only 10 and 25% of the overflow of NE obtained in the presence of PBA at 1 and 5 Hz, respectively, could be accounted for by increased exocytosis. Depletion of tissue NE (80%) by pretreatment with alpha-methyl-p-tyrosine considerably reduced the effectiveness of PBA in enhancing the nerve stimulation-mediated overflow of NE, 3-H-NE, total 3-H and, particularly, of DBH activity. After reserpine treatment, the tissue NE content was reduced by more than 99%, yet the nerve stimulation-mediated release of DBH activity was similar to control spleens. PBA failed to enhance the nerve stimulation-mediated overflow of DBH activity after reserpine treatment. Thus it appears that the enhancement in the exocytotic release of transmitter by nerve stimulation observed in the presence of PBA is related to the concentration of NE in the synaptic space. Therefore, the present study is in favor of the notion that presynaptic alphareceptors may form part of a negative feedback control mechanism by which the transmitter may inhibit its own release.
对分离并灌注的猫脾脏进行电刺激后，发现去甲肾上腺素（NE）、3-H-NE、总3-H以及每神经冲动的多巴胺-β-羟化酶（DBH）活性的溢出呈频率依赖性增加。在所研究的频率范围内，观察到递质溢出和DBH活性呈比例增加，这表明NE胞吐释放的增加是随着刺激频率增加递质溢出增强的主要机制。在来自对照猫和α-甲基-对-酪氨酸处理猫的脾脏中，研究了3μM酚苄明（PBA）对神经刺激介导的NE、总3-H、3-H-NE和DBH活性溢出的影响，刺激频率为1和5Hz。同样，在利血平处理的猫的脾脏中研究了DBH活性的释放。在对照猫的脾脏中，PBA使递质溢出和DBH活性显著增加。这种增强在5Hz时比在1Hz时更明显。据估计，在1Hz和5Hz时，PBA存在下获得的NE溢出中，分别只有10%和25%可归因于胞吐作用增加。用α-甲基-对-酪氨酸预处理使组织NE耗竭（80%），大大降低了PBA增强神经刺激介导的NE、3-H-NE、总3-H，特别是DBH活性溢出的有效性。利血平处理后组织NE含量降低超过99%，但神经刺激介导的DBH活性释放与对照脾脏相似。利血平处理后，PBA未能增强神经刺激介导的DBH活性溢出。因此，似乎在PBA存在下观察到的神经刺激引起的递质胞吐释放增强与突触间隙中NE的浓度有关。因此，本研究支持这样一种观点，即突触前α受体可能构成负反馈控制机制的一部分，通过该机制递质可抑制其自身释放。
