A possible role as a neuromodulator of extraneuronally released-ATP.

可能作为神经元外释放的 ATP 的神经调节剂。

• 批准号: 02670102
• 负责人: KATSURAGI Takeshi
• 金额: $ 1.41万
• 依托单位: Fukuoka University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670102/
• 关键词: guinea-pig; vas deferens; ileum; atrium; ATP; transmitters' receptor stimulation; postjunctional release; transsynaptic neuromodulation; 非神経性ATP遊離; ATP誘発性ATP遊離機構; モルモット回腸縦走節; モルモット精管; シナプス横断性神経伝達調筋; 電位依存性カルシウムイオンチャネル開放

The research project on the above title to 1991 from 1990 was attempted to elucidate further characteristics and physiological roles of extraneurofial ATP release from smooth and cardiac muscles of guinea-pig. Amounts of ATP and ACh in sample media were measured -by a luciferi. n-luciferase assay and HPLC-ECD system, respectively. This report is mainly composed of the following three contents. 1. ATP release from smooth muscles : ATP releases from the vas deferens and ileum were effectively caused by NA and ACh, respectively, compared to other receptor agonists such as substance P. - The evo-ked-ATP release was markedly prohibited by respective receptor antagonists, i. e., prazosin and atropine. alpha, beta-Methylene ATP (alpha, beta-mATP), a P_2-agonist, also produced a suramin (P_2-antagonist) sensitive ATP release from these tissues, indicating the existence of ATP evoked-ATP release system. There seems to be a coupling mechanism between transmitters' receptor stimulation and postju … More nctional ATP release in smooth muscles. 2. ATP release from cardiac muscles : Cardiotonics, e. g., isoproterenol, (Iso), markedly enhanced the contraction and the subsequent ATP release. The enhancement by Iso of ATP release was antagonized by propranolol, but not by butoxamine, a beta_2-antagonist, thus, showing that the origin of the release seems to be, primarily, postjunctional sites. 3. Roles of extraneuronally released-ATP : Electrically evoked-ACh release from the ileal preparation was reduced by alpha, beta-mATP as well as adenosine. As stated above, since alpha, beta-mATP per se elicited the ATP release, the released ATP is enzymatically changed to adenosine and the nucleoside may modulate the neurotransmission. ATP produced a contraction coupled with activation of Ca^<2+>-influx in smooth muscles. Both the responses were completely blocked by nifedipine, a Ca^<2+>-antagonist, implying an activation by ATP of voltage gated-Ca^<2+>-channels. In conclusion, there is an extraneuronal ATP release which is elicited by activating transmitters' receptors in smooth and cardiac muscles and the released ATP may serve as a neuromodulator or a neurostimulator in autonomic neurotransmission. Less

本课题从1990年开始至1991年完成，旨在进一步阐明豚鼠平滑肌和心肌神经元ATP释放的特点和生理作用。通过比色法测量样品培养基中ATP和ACh的量。荧光素酶法和HPLC-ECD系统。本报告主要由以下三部分内容组成。1.平滑肌ATP释放：与其他受体激动剂如P物质相比，NA和ACh分别有效地引起输精管和回肠ATP释放。例如，哌唑嗪和阿托品。P_2激动剂α，β-亚甲基ATP（α，β-mATP）也能产生P_2拮抗剂苏拉明（suramin）敏感的ATP释放，表明存在ATP诱发的ATP释放系统。递质受体兴奋与后应激之间可能存在耦合机制 ...更多信息 平滑肌的ATP释放。2.心肌ATP释放：强心药，e。例如，在一个实施例中，异丙肾上腺素（Iso）可显著增强收缩和随后的ATP释放。Iso对ATP释放的促进作用可被普萘洛尔所拮抗，但不被β_2-受体拮抗剂butoxamine所拮抗，这表明ATP释放的起源似乎主要是连接后部位。3.神经元释放的ATP的作用：电诱发的乙酰胆碱释放从回肠制备减少α，β-mATP以及腺苷。如上所述，由于α，β-mATP本身引起ATP释放，释放的ATP被酶促转化为腺苷，并且核苷可以调节神经传递。ATP引起平滑肌收缩，同时激活平滑肌中的Ca^2+内流。这两种反应都被钙拮抗剂硝苯地平完全阻断，这意味着ATP激活了电压门控Ca ^<2+>通道。总之，在平滑肌和心肌中，存在通过激活递质受体而引起的神经元ATP释放，释放的ATP可能在自主神经传递中充当神经调节剂或神经刺激剂。少

项目成果

桂木 猛: "シナプスへのATP動員機構ー特に非神経性組織からの遊離についてー" 日本薬理学雑誌(総説特集号). 98. 227-234 (1991)

Takeshi Katsuragi：“ATP 动员到突触的机制 - 特别是从非神经元组织中释放”日本药理学杂志（评论特刊）98. 227-234（1991）。

Katsuragi, T.: "Involvement of dihydropyridine-sensitive Ca^<2+> channels in adenosine-evoked inhibition of acetylcholine release form guinea pig ileal preparation." J. Neurochem. 55. 363-369 (1990)

Katsuragi, T.：“二氢吡啶敏感的 Ca^2 通道参与腺苷诱发的豚鼠回肠制剂中乙酰胆碱释放的抑制。”

S.Usune: "Involvement of K^+ -channel opening in endothelin-1 induced supression of spontaneous contractions in the guinea-pig taenia coli." Can.J.Physiol.Pharmacol.

S.Usune：“内皮素-1 中 K 通道开放的参与诱导了豚鼠大肠杆菌自发收缩的抑制。”

T.Katsuragi: "A possible coupling of postjunctional ATP release and transmitters' receptor stimulation in smooth muscles." Life Sci.46. 1301-1307 (1990)

T.Katsuragi：“平滑肌中结后 ATP 释放和递质受体刺激之间可能存在耦合。”

Tokunaga, T.: "Possible postjunctional origin of ATP release from guinea-pig atrium evoked by isoproterenol, forskolin and ouabain." J. Pharmacol. Exp. Ther.

Tokunaga, T.：“异丙肾上腺素、毛喉素和哇巴因引起的豚鼠心房 ATP 释放的可能起源于连接后。”