多他利嗪对钾离子刺激大鼠海马中[3H] - 5 -羟色胺和[3H] - 乙酰胆碱释放的影响。

Effect of dotarizine on K(+)-stimulated [3H]-serotonin and [3H]-acetylcholine release from rat hippocampus.

Hadjiivanova C, Petkov V D, Maslarov D, Totev A, Panova Y, Belcheva I

Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

Gen Pharmacol. 1997 Jan;28(1):129-32. doi: 10.1016/s0306-3623(96)00177-2.

Abstract

The effect of the diphenylmethyl-piperazine derivative dotarizine on K(+)-stimulated release of [3H]serotonin ([3H]5-HT) and [3H]acethylcholine ([3H]Ach) in rat hippocampal slices was studied. 2. Dotarizine at a concentration of 10(-6) M significantly decreased the basal [3H]5-HT release and, at a concentration of 10(-5) M, it significantly decreased the K(+)-stimulated [3H]5-HT release compared to vehicle controls. 3. Dotarizine, at a concentration of 5 x 10(-7) M, significantly increased both basal and K(+)-stimulated [3H]Ach release. At higher concentrations (10(-6) and 2 x 10(-6) M), dotarizine did not change the basal release but significantly increased the K(+)-stimulated [3H]Ach release. The effect of dotarizine on K(+)-stimulated [3H]Ach release decreased with increasing dotarizine concentrations. 4. It is speculated that, in addition to its Ca2+ antagonistic activity, dotarizine exerts an antagonistic effect on the presynaptic 5-HT autoreceptors, which could account for the facilitation of [3H]Ach release.

摘要

研究了二苯甲基哌嗪衍生物多他利嗪对大鼠海马切片中钾离子刺激的[3H]5-羟色胺（[3H]5-HT）和[3H]乙酰胆碱（[3H]Ach）释放的影响。2. 浓度为10(-6) M的多他利嗪显著降低了基础[3H]5-HT的释放，而浓度为10(-5) M时，与溶剂对照组相比，它显著降低了钾离子刺激的[3H]5-HT释放。3. 浓度为5×10(-7) M的多他利嗪显著增加了基础和钾离子刺激的[3H]Ach释放。在更高浓度（10(-6) 和2×10(-6) M）时，多他利嗪不改变基础释放，但显著增加了钾离子刺激的[3H]Ach释放。多他利嗪对钾离子刺激的[3H]Ach释放的影响随多他利嗪浓度的增加而降低。4. 据推测，除了其钙拮抗活性外，多他利嗪对突触前5-HT自身受体发挥拮抗作用，这可能解释了[3H]Ach释放的促进作用。