Effect of Vesamical and Hemicholinium-3 on the Release of

• Main Authors: Lee,Shu-Hui, 李淑惠
• Other Authors: Chang,Chuan-Chiung
• Format: Others
• Language: zh-TW
• Published: 1993
• Online Access: http://ndltd.ncl.edu.tw/handle/07407707592709659966

碩士 === 國立臺灣大學 === 藥理學研究所 === 81 === 1.於小鼠膈神經─膈膜肌標本，探討干擾乙醯膽鹼(ACh)儲存及合成之 ves- amicol和hemicholinium-3對神經-肌傳遞的影響.除觀察肌收縮反應 外，並運用電生理技術，檢視藥品對微小終板及終板電位的影響；並研究 此二者對抑制神經傳遞物水解所產生之再生性ACh釋放及攣縮凋萎的影響 。2.Ves- amicol(0.3∼7.mu.M)與hemicholinium-3(0.1∼10.mu.M)不改 變直接刺激收縮反應，對單一間接刺激之膈肌收縮亦無影響。若配合以 每5分鐘100Hz為時5秒間接刺激的情況下，高濃度vesamicol(7.mu.M)及 hemicholinium-3 (10.mu.M)則明顯抑制單一及強直肌收縮反應。 3.Vesamicol及hemicholi- nium-3抑制因neostigmine所增加之單一肌收 縮，且改善neostigmine所致之攣縮凋萎。4.在小雞二頸肌標本，高濃度 hemicholinium-3(3∼10.mu.M)可抑制間接刺激肌收縮，並抑制外加ACh引 起之攣縮反應，但vesamicol則否。5.於小鼠膈神經－膈膜肌標本，高濃 度vesamicol(7.mu.M)與hemicho- linium-3(10.mu.M)些許抑制微小終板 電位振幅，vesamicol增加其出現頻率。6.於.mu.-conotoxin 或切割方式 麻痺之神經-肌標本，vesamicol不影響終板電位振幅，而高濃 度 hemicholinium-3也僅些微抑制。7.以上vesa- micol及hemicholinium-3 對 微小終板及終板電位振幅之抑制作用會因給予高頻間接刺激而更加強 ， 兩者也會加深連續刺激時終板電位衰減。8.從 .mu.-conotoxin處理之 標本，vesamicol(7.mu.M)於高頻刺激後會減少終板電位量子釋放。不過 在高頻刺激下vesamicol與hemicholinium-3兩者均顯著減少immediately available release pool約50％。9.前處理neostig- mine之標本， vesamicol與hemicholinium-3均可減少微小終板及單一終板電位振幅、縮 短幅寬，給予高頻刺激後更為顯著。至於對neostigmine下高頻刺激，引 起之再生性ACh釋放，兩者均可減少其發生機率；於仍可產生此釋放之終 板，對鍵後終板區持續去極化之振幅及持期則無或僅只輕微影響。10.綜 合結論如下：Vesamicol及hemicholinium-3可經由干擾神經末梢 ACh之合 成及儲存而減少單一量子單位，此外亦會經由減少immediately available pool及抑制mobilization，而產生攣縮凋萎及阻礙再生性ACh 釋放。由於其抑制再生性去極化之作用與其減少微小終板及終板電位有多 項差異，顯示此再生性ACh之來源與負責供應當神經興奮時量子釋放所需 之 vesicle pool有所不同。 1.The effects of vesamicol and hemicholinium-3 on the release of neurotransmitter, were examined in mouse phrenic nerve- diaphragms by measuring muscle contractions, endplate potentials(EPPs),mini- ature endplate potentials(MEPPs) and prolonged regenerative depo- larizations.2.When stimulated indirectly with pulses at 100Hz for 5 sec every 5 min, vesamicol or hemicholinium-3 progressively in- hibited tetanic contractions in pulse-dependent manner.3.In dia- phragms pretreated with 0.3.mu.M neostigmine, vesamicol and hemi- cholinium-3 reversed the twitch responses and significantly anta- gonized the tetanic fade.4.Upon periodic train stimulations, both vesamicol and hemicholinium-3 inhibited the MEPP amplitued by about 30% in the absence or presence of neostigmine.5.The effects of vesamicol and hemicholinium-3 on the amplitude of EPPs evoked by single pulses (0.5Hz) in diaphragm preparations, treated with .mu.-conotoxin or cut to inactivate sodium channel, were similar to those on MEPP exceot that, after repeated train stimulations, vesamicol (but not hemicholinium-3) depressed the amplitude of EPP more significantly than of MEPP (60 vs. 30%), suggesting a reduction of quantal release by vesamicol.6.Both vesamicol and hemicholinium-3 significantly reduced the occurrence of regenera- tive acetylcholine release during repetitive stimulations.7.In conclusions, vesamicol and hemicholinium-3 decreased the acetyl- choline release by reducing the quantal size after periodic train stimulations.According to the observations of vesamicol and hemi- cholinium-3 on prolonged depolarization of endplate, it is sugge- sted that the source of acetylcholine for regenerative release is different from that released under normal physiological