Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
Neuroscience. 2017 Sep 30;360:18-27. doi: 10.1016/j.neuroscience.2017.07.043. Epub 2017 Jul 28.
The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1μM) was ineffective on the mEPSCs, and the highest concentration (100μM) exerted a stronger inhibitory effect. L-DOPA (10μM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical stimulation of the tractus solitarius and increased the paired-pulse ratio. The inhibitory effects of L-DOPA on mEPSCs and eEPSCs were similar to those of dopamine (100μM). The effects of L-DOPA were blocked by a competitive antagonist, L-DOPA methyl ester (100μM) and also by a D receptor antagonist, sulpiride (10μM), while those of dopamine were blocked by the latter but not by the former. In reserpine (5mg/kg, s.c.)-treated rats, the effects of L-DOPA on both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained unchanged. The present results suggest a possibility that L-DOPA may induce the release of dopamine from the axon terminals in the NTS and the released dopamine suppresses the glutamatergic transmission through activation of the presynaptic D receptors.
用大鼠脑片研究了 L-DOPA 对孤束核(NTS)二级神经元兴奋性突触传递的作用方式。L-DOPA(10μM)的灌流减少了微小兴奋性突触后电流(mEPSCs)的频率,而对幅度没有任何影响。低浓度(1μM)对 mEPSCs 无效,而最高浓度(100μM)则产生更强的抑制作用。L-DOPA(10μM)降低了孤束束刺激诱发的 EPSCs(eEPSCs)的幅度,并增加了成对脉冲比。L-DOPA 对 mEPSCs 和 eEPSCs 的抑制作用与多巴胺(100μM)相似。L-DOPA 的作用被竞争性拮抗剂 L-DOPA 甲酯(100μM)和 D 受体拮抗剂舒必利(10μM)阻断,而多巴胺的作用被后者阻断,但不受前者阻断。在利血平(5mg/kg,sc)处理的大鼠中,L-DOPA 对 mEPSCs 和 eEPSCs 的作用完全被阻断,但多巴胺的作用不变。本研究结果表明,L-DOPA 可能通过激活轴突末梢的 D 受体,从 NTS 中的轴突末梢释放多巴胺,从而抑制谷氨酸能传递。