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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 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
批准号:
10470026
负责人:
GOSHIMA Yoshio
金额:
$8.32万
依托单位:
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
项目状态:
已结题
起止时间:
1998 至 1999

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中文摘要
翻译
[I]L多巴在压力感受性反射中的作用:[1](1)电解损毁右侧孤束核,选择性地使同侧延髓尾侧腹外侧腹外侧区L多巴的组织含量减少45%。(2)反复、持续地间歇刺激右主动脉降压神经,引起L多巴的释放、低血压和心动过缓。急性损毁同侧孤束核可抑制L-多巴酚丁酸的释放。[2]在分离的孤束核单细胞神经元上,L多巴0.1~1 mM使HVA钙电流增加,最大作用超过对照电流的50%。此作用可被竞争性的L-多巴阻断剂L-多巴甲酯阻断。[II]L-多巴作为脑缺血迟发性神经细胞死亡的偶然因素的鉴定:四支血管阻断造成的短暂性脑缺血10min使大鼠纹状体微透析过程中细胞外L-多巴、多巴胺和谷氨酸含量增加,并导致神经细胞死亡。在缺血前10min,纹状体内灌流竞争性多巴受体拮抗剂L-多巴转运体环己酯,呈浓度依赖性地减少谷氨酸释放而不改变多巴胺的释放,并保护神经元免于细胞死亡。[III]L多巴转运体:(1)在非洲爪哇卵母细胞中,注射兔肠上皮多聚酶A+核糖核酸,观察到L-[14C]多巴转运体具有高亲和力的转运活性。这种摄取部分依赖于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。联合注射反义cRNA和与兔rBAT互补的寡核苷酸几乎完全抑制卵母细胞对L-[14C]DOPA的摄取。因此,rBAT负责L-[14C]DOPA的摄取活性。
英文摘要
[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.
期刊论文(31)
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科研奖励(0)
会议论文
古川信也、新井信隆、三須良實: "ドーパはグルタミン酸遊離-神経細胞死の上流因子か「ニューロン死を標的とした神経疾患治療薬」" 医学のあゆみ. 186. 791-795 (1998)
Shinya Furukawa、Nobutaka Arai、Yoshimi Misura:“DOPA 是谷氨酸释放神经元细胞死亡的上游因素吗?‘针对神经元死亡的神经系统疾病治疗药物’”《医学史》186. 791-795 (1998)。
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通讯作者:
Goshima Y.Honjo K et al.: "The evidence for tonic GABA ergic regulation of basal L-DOPA release viaactivation of inhibitory GABAA recepters in the nucleas tractus sclitarii of anesthetized rats."Neurosci.Lett.. 261. 155-158 (1999)
Goshima Y.Honjo K 等人:“通过激活麻醉大鼠巩膜核中的抑制性 GABAA 受体,对基础 L-DOPA 释放进行强直性 GABA 能调节的证据。”Neurosci.Lett.. 261. 155-158 (1999)
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Honjo K. et al,: "GABA may function via GABAA receptors to inbibit hypotension and brady cardia by L-DOPA microinjected into depressor sipes of the nucleus tranctus solitari in anestherized rats"Neurosci Lett.. 261. 93-96 (1999)
Honjo K. 等人:“GABA 可能通过 GABAA 受体发挥作用,通过将 L-DOPA 显微注射到麻醉大鼠孤束核的降压刀槽纹中来抑制低血压和心动过缓”Neurosci Lett.. 261. 93-96 (1999)
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Nishiyama M.Miyamae T et al.: "An L-DOPA ergic relay from the posterior hypothalamic nucleu's to the rostral ventrolateral medulla and its cardiovascular function in anesthetizrats."Neuroscience. 92. 123-135 (1999)
Nishiyama M.Miyamae T 等人:“从下丘脑后核到延髓头端腹外侧核的左旋多巴能传递及其在麻醉大鼠中的心血管功能。”神经科学。
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共 31 条
    Roles of L-DOPA as a neurotransmitter and L-DOPA reuptake systems involved
    • 批准号:
      18H02580
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.23万
    • 财政年份:
      2018
    • 负责人:
      GOSHIMA Yoshio
    • 依托单位:
    Functional analysis of DOPAergic transmission in cardiovascular system
    • 批准号:
      15H04687
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.23万
    • 财政年份:
      2015
    • 负责人:
      GOSHIMA Yoshio
    • 依托单位:
    Functional of GPR143, a novel G protein-coupled receptor for L-DOPA
    • 批准号:
      24390062
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.98万
    • 财政年份:
      2012
    • 负责人:
      GOSHIMA Yoshio
    • 依托单位:
    Identification of novel DOPA ligands and electrophysiological analysis of DOPA-induced response
    • 批准号:
      20300132
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.56万
    • 财政年份:
      2008
    • 负责人:
      GOSHIMA Yoshio
    • 依托单位:
    海外基金