- 作者: 蕭水銀;符文美
- 作者服務機構: 國立臺灣大學醫學院藥理研究所
- 中文摘要: 正當我們研究心?毒素(cardiotoxin)之作用機構時,發現鈣離子不但抑制心?毒素之與細胞膜結合,而且抑制心?毒 素的許多藥理作用,鑑於鈾離子對細胞膜鈣離子結合處之親和力很?,我們曾試驗紬離子紫?心?毒素之藥理作用的影響,結 果發現鈾離子果然比鈣離子更?,如拮抗心?毒素之直接溶血作用及對HeLa cell之致毒作用。本篇論文研究的目的,除了 試驗鈾離子對心?毒素引起小雞頸肌攣縮作用之影響外,其對神經腱前毒素(β-bungarotoxin)之阻斷神經一肌傳導作用之 影響也一併研究,因β-bungarotoxin之藥理作用也可能與改變細胞膜對鈣離子滲透性之作用有關。而鈾離子對其他神經毒 或藥物之作用的影響也加以研究,做?對照試驗,以期顯現鈾離子作用之特殊專一性。 由實驗結果,得知鈾離子對β-bungarotox?n之阻斷神經-肌傳導之作用及心?毒素之攣縮作用具有特殊的拮抗作用,因 鈾離子對其他毒素或藥物之作用無顯著影響,如神經腱後毒素(cobrotoxin及α-bungarotoxin),河豚毒素(tetrodotoxin) 及procaine之阻斷神經-肌傳導作用,及乙醯膽鹼(acetylcholine) , high K+, protoveratrine A, melittin之攣縮作用皆 不受鈾離子拮抗,相反地,Caffeine引起之攣縮作用可?鈾離子加?。 進一步研究鈾離子拮抗β-bungarotox?n之作用機構,我們發現鈾離子不但抑制β-bungarotoxin之結合而且抑制β-bungarotoxin結合後?生作用的步驟,β-bungarotoxin與小雞頸肌作用10分鐘後,將β-bungarotoxin洗掉,結果?生 神經-肌傳導阻斷作用與不洗掉之作用相差不多,表示β-bungarotoxin在10分鐘內不可逆結合幾乎完全,常鈾離子與β-bungarotox?n一齊加入,二者於10分鐘後一起洗掉則?生的神經-肌傳導之阻斷作用比β-bungarotox?n單獨作用時稍弱, 顯示鈾離子,對β-bungarotoxin之結合於小雞頸肌有默抑制作用,若鈾離子在/3-bungarotoxin洗掉後加入,則拮抗β-bungarotox?n之神經-肌傳導之阻斷作用更明顯,顯示鈾離子對β-bungarotoxin?生作用之階段具有明顯的抑制,若鈾離 子先處理小雞頸肌20分鐘後,再加β-bungarotoxin , 二者皆不洗掉,則鈾離子拮抗β-bungarotoxin之作用最明顯,此種 作用與鈾離子拮抗β-bungarotoxin之致毒作用之關係將討論之。
- 英文摘要: Owing to its high affinity to the Ca++ binding sites, UO2++ has been tested to see if it can affect the pharmacological actions of cardiotoxin. In accordance with our working hypothesis that cardiotoxin induced pharmacological actions primarily by binding to the Ca++ sites and releasing the membrane-bound Ca++, UO2++ antagonized cardiotoxin not only in inducing direct hemolysis but also the cytotoxic action on HeLa cells. A further study on the effect of UOa++ on cardio-toxin contracture was carried out in this paper. UO2++ antagonized specifically cardiotoxin but not acetylcholine, high K+, protoveratrine A and melittin in inducing a contracture of the chick biventer cervicis muscle. Caffeine contracture was, however, potentiated by UO2++. On the other hand, UO2++ antagonized the neuromuscular blocking action of β-bungarotoxin but not that of cobrotoxin, α-bungarotoxin, tetrodotoxin and procaine. Both binding of β-bungarotoxin and that followed by the changes inducing the neuromuscular blockade were antagonized by UO2++. The possible mechanism of specific antagonism by UO2++ on cardiotoxin and β-bungarotoxin was discussed in terms of the alteration of membrane Ca++ transport.
- 中文關鍵字: --
- 英文關鍵字: --