Cardinali D P, Nagle C A, Freire F, Rosner J M
Neuroendocrinology. 1975;18(1):72-85. doi: 10.1159/000122385.
Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump.
将大鼠下丘脑富含突触体的匀浆与褪黑素进行预孵育，导致去甲肾上腺素、5-羟色胺、多巴胺和谷氨酸摄取显著减少。褪黑素的抑制作用是非竞争性的；初始摄取过程的表观Km值分别为：去甲肾上腺素(2.5±0.3)×10(-7)M、5-羟色胺(2.6±0.3)×10(-7)M、多巴胺(2.4±0.4)×10(-7)M和谷氨酸(1.0±0.3)×10(-7)M。褪黑素抑制递质摄取的表观Ki值分别为：0.64±0.14mM（去甲肾上腺素）、0.23±mM（5-羟色胺）、0.51±0.08mM（多巴胺）和1.21±0.10mM（谷氨酸）。通过将培养基中[K+]增加到30mM诱发的递质释放，褪黑素以剂量依赖性方式增强。对5-羟色胺释放观察到最大效应。富含突触体的匀浆中3H-褪黑素的积累在0℃和37℃之间未表现出差异，表明该激素的摄取不是一个主动过程。这些结果表明，外源性给予的褪黑素可能通过改变递质摄取机制而非与递质竞争其摄取泵来影响下丘脑神经递质积累和释放。
