Nicol B, Rowbotham D J, Lambert D G
University Department of Anaesthesia, Leicester Royal Infirmary, UK.
Neurosci Lett. 1996 Nov 1;218(2):79-82. doi: 10.1016/s0304-3940(96)13104-9.
We have examined the effects of a range of opioid receptor subtype selective agonists on K+ evoked glutamate release from perfused rat cerebrocortical slices. Dual application (S1 and S2) of K+ (46 mM) evoked dual monophasic glutamate release profiles. When areas under the release curves were calculated an S2/S1 ratio for control slices of 1.07 +/- 0.08 (n = 75) was obtained, this was reduced by 80% with EGTA (0.1 mM) treatment confirming the presence of a Ca2+ regulated release process, Morphine produced a dose-dependent inhibition of the S2/S1 ratio. At 1 microM this amounted to 78 +/- 12% (mean +/- SEM; n = 6). (D-Ala2,MePhe4,gly(ol)5)enkephalin (DAMGO; 60 +/- 12%, n = 6 at 1 microM), and spiradoline (53 +/- 14% at 1 and 71 +/- 11% at 100 microM, both n = 6) also inhibited glutamate release in a cyprodime (10 microM) and norbinaltorphimine (10 microM) reversible manner. (D-Pen2.5) enkephalin (DPDPE; 1 microM) was ineffective. All agents tested did not affect basal glutamate release. Collectively these data implicate a role for mu and kappa opioids in the control of evoked glutamate release and their potential for neuroprotective therapy.
我们研究了一系列阿片受体亚型选择性激动剂对钾离子诱发的灌流大鼠大脑皮质切片中谷氨酸释放的影响。钾离子（46 mM）的双重应用（S1和S2）诱发了双重单相谷氨酸释放曲线。计算释放曲线下面积时，对照切片的S2/S1比值为1.07±0.08（n = 75），用乙二醇双四乙酸（EGTA，0.1 mM）处理后该比值降低了80%，证实存在钙离子调节的释放过程。吗啡对S2/S1比值产生剂量依赖性抑制。在1 μM时，抑制率达78±12%（平均值±标准误；n = 6）。（D-丙氨酸2，甲硫氨酸4，甘醇5）脑啡肽（DAMGO；1 μM时为60±12%，n = 6）和spiraoline（1 μM时为53±14%，100 μM时为71±11%，均n = 6）也以一种可被环丙甲羟二氢吗啡酮（10 μM）和去甲二氢吗啡酮（10 μM）逆转的方式抑制谷氨酸释放。（D-青霉胺2.5）脑啡肽（DPDPE；1 μM）无效。所有测试药物均不影响基础谷氨酸释放。总体而言，这些数据表明μ和κ阿片类药物在控制诱发的谷氨酸释放中起作用，以及它们在神经保护治疗方面的潜力。
