Mechanism of the transmitter release facilitation through activation of presynaptic ATP receptors in the brainstem

通过激活脑干突触前 ATP 受体促进递质释放的机制

• 批准号: 13680902
• 负责人: KATO Fusao
• 金额: $ 1.98万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680902/
• 关键词: nucleus tractus solitarii; brain slice; patch-clamp; postsynaptic current; adenosine 5 ' -triphosphate; P2X receptor; glutamate release; presynaptic ligand-gated channels

P2X receptors (P2X-Rs) are ATP-gated channels permeable to cations inclining Ca^<2+>. We recorded miniature excitatory postsynaptic currents (mEPSCs) under blockade of voltage-dependent Na^+ channels from second-order neurons in the nucleus tractus solitarii in vitro, a part of the brain where exogenous ATP has profound effects on autonomic outflow. Activation of presynaptic P2X-Rs with ATP or α,β-methylene ATP (α,βmATP) not only enhanced the release of glutamate, but could initiate it de novo even when voltage-dependent calcium channels (VDCCs) were completely blocked. This facilitating effect of αβmATP on the glutamate release was abolished completely by a P2X-R antagonist pyridoxalphosphate-6-azophenyl-2',4' -disulphonic acid (PPADS) and by a high, but not a low, concentration of a subtype-selective antagonist 2 > ,3 ' -O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP). Despite manifest increase in the frequency of excitatory postsynaptic events by αβmATP, the rate of the synaptic failures as evaluated by solitary tract stimulation was not significantly affected. The miniature excitatory postsynaptic potentials elicited with P2X-R agonists recorded under blockade of VDCC-dependent synaptic transmission were sufficient to trigger action potentials in the postsynaptic cell. These results show that a rise in extracellular ATP concentration promotes excitatory transmission even in the absence of presynaptic excitation, leading to a consequent activation of the autonomic networks.

P2X 受体 (P2X-R) 是 ATP 门控通道，可渗透倾向于 Ca^2+ 的阳离子，我们记录了在细胞核中二级神经元的电压依赖性 Na^+ 通道阻断下的微型兴奋性突触后电流 (mEPSC)。体外孤束，外源 ATP 对突触前自主神经流出具有深远影响的大脑部分。具有 ATP 或 α,β-亚甲基 ATP (α,βmATP) 的 P2X-R 不仅可以增强谷氨酸的释放，而且即使在电压依赖性钙通道 (VDCC) 完全阻断时也可以从头启动谷氨酸的释放。 P2X-R 拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸完全消除了对谷氨酸释放的影响(PPADS) 和高浓度而不是低浓度的亚型选择性拮抗剂 2>,3'-O-(2,4,6-三硝基苯基)-ATP (TNP-ATP)。 αβmATP 兴奋性突触后事件的频率，通过孤束刺激评估的突触失败率没有显着影响。在 VDCC 依赖性突触传递阻断下记录的 P2X-R 激动剂足以触发突触后细胞中的动作电位。这些结果表明，即使在没有突触前兴奋的情况下，细胞外 ATP 浓度的升高也会促进兴奋性传递，从而导致随后的激活。的自主网络。

项目成果

Nishi H, Kato F, Masaki E, Kawamura M: "ADP-sensitive purinoceptors induce steroidogenesis via adenylyl cyclase activation in bovine adrenocortical fasciculata cells"Brit J Pharraacol. J137. 177-184 (2002)

Nishi H、Kato F、Masaki E、Kawamura M：“ADP 敏感嘌呤受体通过牛肾上腺皮质束状细胞中的腺苷酸环化酶激活诱导类固醇生成”Brit J Pharraacol。

Kawamura M, Masaki E, Kato F: "Regulation of inhibitory synaptic transmission by cholinoceptors in the brainstem nociceptive network of the rat"The 3rd International Symposium on the Study of Brain Function Abstracts. 213 (2002)

Kawamura M、Masaki E、Kato F：“大鼠脑干伤害性网络中胆碱受体对抑制性突触传递的调节”第三届国际脑功能研究研讨会摘要。

Kawamura M, Tanaka J. Inoue K, Kato F: "Rat kaiba CA3 suitai saibou heno kohunsei oyobi yokuseisei shinapusu nyuuryoku ni oyobosu saibougai ATP no souhantekisayou (in Japanese)"Shinkei-Kagaku. 40 (2&3). 437 (2001)

Kawamura M、Tanaka J. Inoue K、Kato F：“Rat kaiba CA3suitai saibou heno kohunsei oyobi yokuseisei shinapusu nyuuryoku ni oyobosu saibougai ATP no souhantekisayou（日语）”Shinkei-Kagaku。

Masaki E, Kawamura M, Kato F: "Reduction by sevoflurane of adenosine 5'-triphosphate-activated inward current of locus coeruleus neurons in pontine slices of rats"Brain Research. 921. 226-232 (2001)

Masaki E、Kawamura M、Kato F：“通过七氟烷减少 5-三磷酸腺苷激活的大鼠脑桥切片中蓝斑神经元的内向电流”大脑研究。

Kato F: ""Hitotsubu de nido oishi" saibou-gai messenger to shiteno ATP - Saibou-gai ATP to purine juyotai niyoru nounai shiiiapusu dentatsu no taju-seigyo (in Japanese)"No-kinou No Kaimei - Seimei Kagaku no Syuchoryuu- eds.Akaike, Higashi, Abe, Kubo.Gaiya

加藤 F：““Hitotsubu de nido oishi”saibou-gai Messenger tooshiten ATP - Saibou-gai ATP to purine juyotai niyoru nounai shiiiapusu dentatsu no taju-seigyo（日文）”No-kinou No Kaimei - Seimei Kagaku no Syuchoryuu-eds