Reimann W, Köllhofer U
Gödecke Research Institute, Freiburg, FRG.
Pharmacology. 1988;36(4):249-57. doi: 10.1159/000138391.
In rat cerebral cortex slices we investigated the Ca2+ dependency of noradrenaline release and the influence of inorganic and organic Ca2+ antagonists. Slices were preincubated with 3H-noradrenaline and then superfused with noradrenaline-free medium. Release of 3H-noradrenaline was elicited by electrical pulses. The stimulation-evoked release was dependent on the external Ca2+ concentration and was inhibited by Cd2+, Co2+ and Mg2+ in a concentration-related manner. These results indicate that electrically stimulated noradrenaline release depends on the Ca2+ influx after opening of voltage-sensitive Ca2+ channels. Organic Ca2+ antagonists were used in concentrations which had no major influence on the basal release rate. Of the drugs tested (bepridil, diltiazem, flunarizine, nimodipine, isradipine, prenylamine, verapamil) only flunarizine and nimodipine showed a minor inhibition of the stimulation-evoked release, which was less than 20% at 1 mumol/l. With nimodipine 10 mumol/l, there was a 6% facilitation of release. All other drugs except flunarizine and verapamil caused a slight facilitation of the stimulation-evoked release. The results provide evidence that the organic Ca2+ channel antagonists investigated do not or only minimally interfere with the noradrenergic nerve terminal Ca2+ channels in a tissue slice preparation. The release-facilitating effects of most organic Ca2+ antagonists cannot be interpreted by the present results.
在大鼠大脑皮层切片中，我们研究了去甲肾上腺素释放对钙离子的依赖性以及无机和有机钙离子拮抗剂的影响。将切片用³H - 去甲肾上腺素预孵育，然后用不含去甲肾上腺素的培养基进行灌流。通过电脉冲引发³H - 去甲肾上腺素的释放。刺激诱发的释放依赖于细胞外钙离子浓度，并被镉离子、钴离子和镁离子以浓度相关的方式抑制。这些结果表明，电刺激引起的去甲肾上腺素释放依赖于电压敏感性钙离子通道开放后的钙离子内流。使用的有机钙离子拮抗剂浓度对基础释放速率没有重大影响。在所测试的药物（苄普地尔、地尔硫䓬、氟桂利嗪、尼莫地平、伊拉地平、普尼拉明、维拉帕米）中，只有氟桂利嗪和尼莫地平对刺激诱发的释放有轻微抑制，在1μmol/L时抑制率小于20%。使用10μmol/L的尼莫地平时，释放增加了6%。除氟桂利嗪和维拉帕米外，所有其他药物均导致刺激诱发的释放略有增加。结果表明，所研究的有机钙离子通道拮抗剂在组织切片制备中不会或仅极少干扰去甲肾上腺素能神经末梢的钙离子通道。大多数有机钙离子拮抗剂的释放促进作用无法用本研究结果来解释。
