Heepe P, Starke K
Br J Pharmacol. 1985 Jan;84(1):147-55.
Slices of rabbit cerebral cortex were preincubated with [3H]-noradrenaline and then superfused and stimulated electrically twice for 2 min each (S1, S2) at various frequencies (0.2-3 Hz). The stimulation-evoked overflow of tritium (S1) increased with increasing frequency and was higher when cocaine (10 microM) was present. In the absence of cocaine, tetraethylammonium (TEA; 100 and 300 microM), added before S2, increased the stimulation-evoked overflow of tritium to about the same extent, irrespective of the frequency. In contrast, rauwolscine (0.1 and 1 microM) and idazoxan (0.1-10 microM) increased the evoked overflow much more, the higher the frequency of stimulation. Phentolamine (0.1 and 1 microM) reduced the overflow elicited at 0.3 and 1 Hz, and (1 microM) caused an increase only at 3 Hz. In slices superfused throughout with cocaine 10 microM, rauwolscine (1 microM) and idazoxan (1 and 10 microM) again increased the evoked overflow of tritium more, the higher the frequency of stimulation. For a given frequency, rauwolscine and idazoxan enhanced the evoked overflow to a greater extent in the presence than in the absence of cocaine. Idazoxan (1 and 10 microM) and rauwolscine (1 microM) counteracted the inhibition that phentolamine (0.1 microM) produced at low frequency. The increases caused by rauwolscine (1 microM) and TEA (300 microM) were approximately additive, but those caused by rauwolscine (1 microM) and idazoxan (10 microM) were not. The effects of rauwolscine, idazoxan and phentolamine depend on the experimental conditions (frequency, cocaine) in a manner compatible with the operation of a presynaptic alpha 2-adrenoceptor-mediated autoinhibition of noradrenaline release. When given at sufficient concentrations, these antagonists enhance the release of noradrenaline more, the higher the biophase concentration of the transmitter and the stronger, hence, the autoinhibition. In the case of the partial alpha 2-adrenoceptor agonist phentolamine, a low perineuronal noradrenaline concentration even reverses facilitation to inhibition. This pattern differs markedly from the pattern of effects of TEA which increases the release of noradrenaline by a mechanism other than alpha-adrenoceptor blockade.
将兔大脑皮层切片与[3H]-去甲肾上腺素预孵育，然后以不同频率（0.2 - 3Hz）进行两次电刺激，每次刺激2分钟（S1、S2）。刺激诱发的氚溢出（S1）随频率增加而增加，且在存在可卡因（10μM）时更高。在不存在可卡因的情况下，在S2之前添加四乙铵（TEA；100和300μM），无论频率如何，都能将刺激诱发的氚溢出增加到大致相同的程度。相比之下，育亨宾（0.1和1μM）和咪唑克生（0.1 - 10μM）随着刺激频率的增加，诱发的溢出增加得更多。酚妥拉明（0.1和1μM）降低了在0.3和1Hz时诱发的溢出，而（1μM）仅在3Hz时导致增加。在整个过程中用10μM可卡因灌流的切片中，育亨宾（1μM）和咪唑克生（1和10μM）同样随着刺激频率的增加，再次使诱发的氚溢出增加得更多。对于给定频率，育亨宾和咪唑克生在存在可卡因时比不存在时更大程度地增强诱发的溢出。咪唑克生（1和10μM）和育亨宾（1μM）抵消了酚妥拉明（0.1μM）在低频时产生的抑制作用。育亨宾（1μM）和TEA（300μM）引起的增加大致呈相加作用，但育亨宾（1μM）和咪唑克生（10μM）引起的增加并非如此。育亨宾、咪唑克生和酚妥拉明的作用取决于实验条件（频率、可卡因），其方式与突触前α2 - 肾上腺素能受体介导的去甲肾上腺素释放的自身抑制作用相符。当以足够浓度给药时，这些拮抗剂随着递质生物相浓度越高，因此自身抑制越强，去甲肾上腺素的释放增加得越多。对于部分α2 - 肾上腺素能受体激动剂酚妥拉明，低的神经元周围去甲肾上腺素浓度甚至会使促进作用转变为抑制作用。这种模式与TEA的作用模式明显不同，TEA通过α - 肾上腺素能受体阻断以外的机制增加去甲肾上腺素的释放。
