von Kügelgen I, Koch H, Starke K
Pharmakologisches Institut, Universität Freiburg, Germany.
Neuropharmacology. 1997 Sep;36(9):1221-7. doi: 10.1016/s0028-3908(97)00101-9.
The possibility of a P2-receptor-mediated modulation of the release of serotonin in the rat brain cortex was investigated in occipito-parietal slices preincubated with [3H]serotonin and then superfused and stimulated electrically (10 pulses, 1 Hz). Adenosine receptor agonists decreased the stimulation-evoked overflow of tritium at best slightly; the selective A1 agonist N6-cyclopentyl-adenosine caused no change. Several nucleotides had more marked effects: ATP (3-1000 microM), adenosine-5'-O-(3-thiotriphosphate) (3-300 microM) and P1,P5-di(adenosine-5')-pentaphosphate (3-300 microM) decreased the evoked overflow by up to ca 35%. AMP, alpha,beta-methylene-ATP and UTP produced smaller decreases and 2-methylthio-ATP and UMP caused no change. The inhibition by ATP was attenuated both by the P1-receptor antagonist 8-(p-sulphophenyl)-theophylline (100 microM) and by the P2-receptor antagonist suramin (300 microM) but was not changed by indomethacin (10 microM) and NG-nitro-L-arginine (10 microM). We conclude that the release of serotonin in the rat brain cortex is inhibited through presynaptic P1-receptors (which are not A1) as well as P2-receptors. Inhibition of release via P2-receptors has been previously shown for noradrenaline (brain cortex and hippocampus) and dopamine (neostriatum) and, hence, may be widespread. Differences between transmitter systems exist, however, in the degree of their sensitivity to presynaptic P2-receptor-mediated modulation.
在预先用[3H]血清素孵育，然后进行灌流并电刺激（10个脉冲，1Hz）的枕顶叶切片中，研究了P2受体介导调节大鼠大脑皮层血清素释放的可能性。腺苷受体激动剂充其量只能轻微降低刺激诱发的氚溢出；选择性A1激动剂N6-环戊基腺苷未引起变化。几种核苷酸有更显著的作用：ATP（3 - 1000微摩尔）、腺苷-5'-O-(3-硫代三磷酸)（3 - 300微摩尔）和P1,P5-二(腺苷-5')-五磷酸（3 - 300微摩尔）可使诱发的溢出减少高达约35%。AMP、α,β-亚甲基-ATP和UTP产生的减少较小，而2-甲硫基-ATP和UMP则无变化。ATP的抑制作用被P1受体拮抗剂8-(对磺基苯基)-茶碱（100微摩尔）和P2受体拮抗剂苏拉明（300微摩尔）减弱，但吲哚美辛（10微摩尔）和NG-硝基-L-精氨酸（10微摩尔）对其无影响。我们得出结论，大鼠大脑皮层中血清素的释放通过突触前P1受体（非A1）以及P2受体受到抑制。先前已表明，去甲肾上腺素（大脑皮层和海马体）和多巴胺（新纹状体）通过P2受体抑制释放，因此，这种抑制可能很普遍。然而，不同神经递质系统对突触前P2受体介导调节的敏感程度存在差异。
