Török T L, Pauló T, Tóth P T, Nguyen T T, Azzidani A M, Magyar K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
J Pharm Pharmacol. 1987 Oct;39(10):797-802. doi: 10.1111/j.2042-7158.1987.tb05121.x.
A high concentration of selegiline ((-)-deprenyl; 10(-4) M) potentiated low frequency (2 Hz) nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers, and inhibited the postsynaptic response. The transmitter-releasing action of 10(-4) M selegiline was inhibited by a moderate increase of external K+ (23.6 mM). Excess K+ by itself abolished the nerve-evoked release of [3H]noradrenaline but did not increase the resting outflow of radioactivity. Excess Ca2+ (7.5 mM) increased the stimulation-evoked transmitter release. In the presence of excess Ca2+, selegiline (10(-4) M) was effective in increasing the [3H]noradrenaline release in response to nerve-stimulation. Excess Ca2+ partly antagonized the postsynaptic inhibitory action of selegiline. In Ca2+-free, 1 mM EGTA-containing Krebs solution both the nerve-evoked 3H release and the transmitter releasing action of selegiline were abolished in agreement with the 'Ca-hypothesis'. The voltage-dependent K+-channel blocker, 4-aminopyridine (10(-5) M), increased the nerve-stimulation-evoked release of tritium from arteries. If selegiline was also present in the perfusion medium the nerve-evoked transmitter release further increased. 4-Aminopyridine completely antagonized the inhibitory action of selegiline on the postsynaptic contraction.
在存在神经元摄取阻滞剂（可卡因，3×10⁻⁵ M）和非神经元摄取阻滞剂（皮质酮，5×10⁻⁵ M）的情况下，高浓度的司来吉兰（（-）-丙炔苯丙胺；10⁻⁴ M）增强了低频（2 Hz）神经刺激诱发的兔离体主肺动脉中[³H]去甲肾上腺素的释放，并抑制了突触后反应。10⁻⁴ M司来吉兰的递质释放作用被细胞外K⁺适度增加（23.6 mM）所抑制。过量的K⁺本身消除了神经诱发的[³H]去甲肾上腺素释放，但并未增加放射性的静息流出量。过量的Ca²⁺（7.5 mM）增加了刺激诱发的递质释放。在存在过量Ca²⁺的情况下，司来吉兰（10⁻⁴ M）可有效增加神经刺激后[³H]去甲肾上腺素的释放。过量的Ca²⁺部分拮抗了司来吉兰的突触后抑制作用。在不含Ca²⁺、含1 mM乙二醇双四乙酸（EGTA）的 Krebs 溶液中，神经诱发的³H释放和司来吉兰的递质释放作用均被消除，这与“钙假说”一致。电压依赖性K⁺通道阻滞剂4-氨基吡啶（10⁻⁵ M）增加了动脉中神经刺激诱发的氚释放。如果灌注介质中也存在司来吉兰，神经诱发的递质释放会进一步增加。4-氨基吡啶完全拮抗了司来吉兰对突触后收缩的抑制作用。
