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L-DOPA Plays a role as a neurotransmitter regulating blood pressure in the lower brain stem, and endogenously evoked L-DOPA is a casual factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rats

L-DOPA 作为调节下脑干血压的神经递质发挥作用，内源性诱发的 L-DOPA 是大鼠短暂性缺血导致谷氨酸释放和由此导致的延迟性神经元细胞死亡的偶然因素

基本信息

批准号：
10470026
负责人：
GOSHIMA Yoshio
金额：
$ 8.32万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

[I] Function of L-DOPA in baroreceptor reflex:[1] (1) Electrolytic lesions of the right nucleus tractus solitarii selectively decrease by 45 % the tissue content of L-DOPA in the dissected ipsilateral caudal ventrolateral medulla.(2) Intermittent stimulation of the right aortic depressor nerve repetitively and constantly causes L-DOPA release, hypotension and bradycardia.(3) Baroreceptor activation selectively evokes L-DOPA. This L-DOPA release is suppressed by acute lesion in the ipsilateral nucleus tractus solitarii.[2] In a single cell neuron isolated from nucleus tractus solitarii, L-DOPA 0.1 to 1 mM augments HVA Ca2+ current with the maximal effect of 50 % over the control current. The effect is blocked by L-DOPA methyl ester, a competitive L-DOPA antagonist.[II] Identification of L-DOPA as a casual factor for delayed neuronal cell death induced by brain ischemia: Ten-min transient ischemia due to four vessel occlusion increases extracellular L-DOPA, dopamine and glutamate during rat striatal microdialysis, and elicits neuronal cell death. Intrastriatal perfusion of 10-100 nM L-DOPA cyclohexyl ester, a competitive DOPA antagonist, 10 min before ischemia, concentration-dependently decreases glutamate release without modification of dopamine release by ischemia, and protects neurons from cell death.[III] L-DOPA transporter:(1) In Xenopus laevis oocytes, injected with polyA+ RNA from rabbit intestinal epithelium, the transport activity for L-[14C]DOPA with a high affinity is observed. This uptake was partially Na+-dependent but Cl- -independent. L-Tyrosine, -phenylalanine, -leucine and E〜lysine inhibit this transport activity. Coinjection of an antisence cRNA, as well as oligonucleotide complementary to rabbit rBAT cDNA almost completely inhibited the uptake of L-[14C]DOPA in the oocytes. rBAT is thus responsible for the L-[14C]DOPA uptake activity.

[I] L-DOPA 在压力感受器反射中的作用：[1] (1) 右孤束核的电解损伤选择性地使解剖同侧尾部腹外侧延髓中 L-DOPA 的组织含量减少 45%。 (2) 反复、持续地间歇性刺激右主动脉降压神经导致 L-DOPA 释放，低血压 (3)压力感受器激活选择性地诱发L-DOPA。这种左旋多巴的释放受到同侧孤束核急性损伤的抑制。[2]在从孤束核分离的单细胞神经元中，0.1 至 1 mM L-DOPA 可增强 HVA Ca2+ 电流，最大效果比对照电流高 50%。该作用被竞争性左旋多巴拮抗剂左旋多巴甲酯阻断。[II]左旋多巴作为脑缺血引起的延迟性神经元细胞死亡的偶然因素的鉴定：四血管闭塞导致10分钟短暂性缺血，在大鼠纹状体微透析过程中细胞外左旋多巴、多巴胺和谷氨酸增加，并诱发神经元细胞死亡死亡。缺血前 10 分钟，纹状体内灌注 10-100 nM L-DOPA 环己酯（一种竞争性多巴拮抗剂），浓度依赖性地减少谷氨酸释放，而不改变缺血引起的多巴胺释放，并保护神经元免于细胞死亡。[III] L-DOPA 转运蛋白：(1) 在非洲爪蟾卵母细胞中，注射聚 A+ 来自兔肠上皮的RNA，观察到对L-[14C]DOPA具有高亲和力的转运活性。这种吸收部分依赖于Na+，但不依赖于Cl-。 L-酪氨酸、-苯丙氨酸、-亮氨酸和E〜赖氨酸抑制这种转运活性。反义 cRNA 以及与兔 rBAT cDNA 互补的寡核苷酸的共注射几乎完全抑制了卵母细胞中 L-[14C]DOPA 的摄取。因此，rBAT 负责 L-[14C]DOPA 摄取活性。