- 作者: 張傳炯; 周美智; 洪士榮; 邱麗珠
- 作者服務機構: 國立臺灣大學醫學院藥理學研究所
- 中文摘要: 尼古丁(Nicotine)已知對自主神經節有去極化性阻斷作用,然後轉為競爭性阻斷作用。本文研究尼古丁對運動神經-骨骼肌傳遞之影響,並探討其對神經末梢乙醯膽素受體之影響。尼古丁低於33μM可加強刺激神經引起之肌肉收縮,但反而加強箭毒素之神經-肌阻斷,也可抑制100 Hz高頻刺激神經引起之強直性肌肉收縮,而產生tetanic fade在76μM,尼古丁很快的(10分內)產生第一期之抑制作用,隨後(60-90分)才產生第二期之完全阻斷作用,Neostigmine在兩期均能部分恢復尼古丁之阻斷而diaminopyridine則能完全對抗之。43μM以上之尼古丁在30分內可產生終板區最大,但只達10-15 mV之去極化作用,其去極化能維持不降,並可被箭毒素對抗。因直接刺激肌肉收縮反應並不受尼古丁影響,表示上述去極化作用並未產生去極化性阻斷效果。終板電位(0.7 Hz)與微小終板電位振幅均被尼古丁平行地抑制,表示尼古丁作用類似箭毒素為抑制鍵後反應,而對鍵前傳遞物質釋放無影響,因此結論:尼古丁以部份興奮劑方式經由雙機制來阻斷神經-肌傳遞。尼古丁(≧22μM)類似其他乙醯膽素受體拮抗劑對高頻刺激引發之終板電位產生明顯之依序遞降之作用,顯示神經末梢之乙醯膽素受體對尼古丁並不比自主神經結之受體敏感。
- 英文摘要: Nicotine at ≦ 33 μM enhanced the single twitch response to indirect stimulation but potentiatedthe blocking effect of tubocurarine. Failure of tetanic contraction (tetanic fade) occurred on stimulationat 100 Hz. At 76 μM, nicotine induced a first phase rapid (10 min) inhibition of twitch response followedlater (60-90 min) by a second phase complete block. Neostigmine partially restored the response at eitherphase of block whereas diaminopyridine completely antagonized the blockade. The end-plate was depolar-ized maximally by only 10-15 mV within 30 min with 43 μM nicotine. The depolarization was maintainedbut was antagonized by tubocurarine. The twitch response induced by direct stimulation was unchangedindicating no depolarization block ensued. The amplitudes of both EPP (0.7 Hz) and MEPP were markedlydepressed in parallel indicating a curare-like postsynaptic inhibition without an effect on the release oftransmitter. It is concluded that nicotine blocks the neuromuscular transmission by a dual mechanism byits partial agonist action. At higher frequencies of transmission, nicotine (≧ 22μM) also produced a re-markable run-down of EPP just like other receptor antagonists suggesting that the nerve terminal actylcho-line receptors are not particularly sensitive to nicotine as those on the autonomic ganglia.
- 中文關鍵字: nicotine; neuromuscular transmission; depolarization of endplate; acetylcholine recep-tro; nicotinic receptor; end-plate potential
- 英文關鍵字: --