McN-a-343의 家兎 腸片에서의 Muscarine性및 抗 Muscarine性 作用 = Muscarinic and antimuscarinic action of McN-A-343 in isolated rabbit intestinal preparations

국문 초록 (Abstract)

Muscarinic receptor agonist인 McN-A-343의 家兎摘出空腸片에 대한 收縮作用을 仲介하는 receptor type을 알아보고, bethanechol (BCh)에 의한 收縮作用에 대한 McN-A-343의 弛緩作用의 機轉을 推究하기 위해 本 實驗을 實施하였다.
1. McN-A-343 (6.3×10^(-6)∼1.9×10^(-4) M)과 BCh (1.5×10^(-6)∼5.1×10^(-5) M) 모두 用量依存的인 收縮反應을 일으켰다. McN-A-343의 收縮反應은 投與直後 最大 反應을 보인후 약 5분후 原狀態로 回復되었으나 BCh의 收縮反應은 收縮狀態가 繼續 維持되었다.
2. Pirenzepine (1.2×10^(-7) M)이나 atropine (7.4×10^(-9) M)前處理下에서 McN-A-343의 用量反應曲線은 非相競的 抑制樣相을 보였으나 BCh의 用量反應曲線은 右側移動되었다.
3. 비슷한 程度의 收縮을 일으키는 McN-A-343 (6.3×10^(-5)이나 1.9×10^(-4) M)과 BCh (5.1×10^(-6)이나 1.5×10^(-5) M)의 收縮을 50% 抑制하는 atropine 및 pirenzepine의 量 (ID_50)을 구한 結果 atropine의 McN-A-343과 BCh에 대한 ID_50은 各各 2.65±0.42 nM (15∼21例 平均±SE) 및 2.07±0.17 nM (16例 平均±SE)로 비슷하였으나 pirenzepine은 30.2±4.19 nM (8∼10例 平均±SE) 및 246.7±19.28 nM (9∼12例 平均±SE)로 McN-A-343의 收縮效果가 BCh收縮效果에 비해 pirenzepine에 훨씬 더 選擇的으로 抑制되었다.
4. McN-A-343前處理로 BCh收縮效果가 抑制되었으며 BCh (5.1×10^(-6) M)收縮反應을 50%抑制하는 McN-A-343의 量은 13.6±198 nM이었다.
5. BCh (5.1×10^(-6) M이나 1.5×10^(-5) M)의 收縮이 atropine, pirenzepine 및 McN-A-343投與에 의해 弛緩되었다. BCh收縮을 50%弛緩시키는 세 藥物의 量을 구한 結果 各各 0.012±0.0016 μM, 0.31±0.13 μM, 27.1±1.27 μM (7∼8例 平均±SE)로 效力의 크기는 atropine > pirenzepine >> McN-A-343의 順이었다.
6. McN-A-343의 BCh收縮에 대한 pA₂는 5.42였다.
7. α-Adrenoceptor antagonist인 phentolamine (2.6×10^(-6) M) 및 purinergic receptor antagonist인 aminophylline (10^(-4) M)處理하에서 BCh (1.5×10^(-5) M)收縮은 影響받지 않았으며 이때 McN-A-343의 弛緩效果도 影響받지 않았다. Anticholinesterase인 physostigmine에 의한 收縮은 McN-A-343에 의해 弛緩되었으나 histamine에 의해 收縮된 狀態에서 投與한 McN-A-343은 오히려 收縮作用을 나타냈다.
以上의 成績으로 家兎空腸片에서 McN-A-343收縮은 BCh收縮보다도 pirenzepine에 銳敏하게 抑制되며, McN-A-343의 BCh收縮에 대한 弛緩作用은 McN-A-343이 muscarinic receptor에 대한 antagonist (partial agonist)로 作用하므로서 일어난다고 推論하였다.

다국어 초록 (Multilingual Abstract)

McN-AMcN-A-343 has been known as an agonist on muscarinic receptor. This study is to delineate the type of muscarinic receptor through which tile contractile response to McN-A-343 was elicited and to elucidate the mechanism involved in its relaxing action on the BCh-induced contractions in rabbit jejunal strips.
1. Both McN-A-343 (6.3×10^(-6)∼1.9×10^(-4) M) and BCh (1.5×10^(-6)∼5.1×10^(-5) M) induced dose-dependent contractions. The McN-A-343-induced contraction spontaneously relaxed to tile basal level about 5 min but Bch-induced contraction was persistently maintained.
2. The pretreatment with pirenzepine (1.2×10^(-7) M) and atropine (7.4×10^(-9) M) non-competitively inhibited the dose-contractile response curve of McN-A-343 but competitively inhibited that of BCh.
3. The concentrations of atropine and pirenzepine which inhibited the contractions induced by McN-A-343 (6.3×10^(-5) or 1.9×10^(-4) M) and BCh (5.1×10^(-6) M or 1.5×10^(-5) M) by 50% (ID_50) were calculated. The ID_50s of atropine to the McN-A-343 and BCh-induced contractions showed no difference (2.65±0.42 and 2.07±0.17 nM respectively) but ID_50 of pirenzepine to McN-A-343-induced contraction was significantly smaller than that to BCh-induced contraction (30.2±4.19 and 246.7±19.28 respectively).
4. Pretreatment with McN-A-343 inhibited the BCh-induced contractions and the concentration of McN-A-343 which produced 50% inhibition of 5.1×10^(-6) M BCh-induced contraction was 13.6±198 nM.
5. Atropine, pirenzepine and McN-A-343 relaxed the contractions induced by BCh (5.1×10^(-6) M and 1.5×10^(-5) M). The concentrations of atropine. pirenzepine and McN-A-343 which relaxed the BCh-induced contractions to 50% were 0.012±0.0016, 0.31±0.13 and 271±1.27 μM, respectively.
6. The pA₂ value of McN-A-343 to BCh-induced contraction was 5.42.
7. Pretreatment with phentolamine (2.6×10^(-6) M), an α-adrenoceptor antagonist, and aminophylline (10^(-4) M), a purinergic receptor antagonist had no effect on the BCh-induced contraction and the relaxing action of McN-A-343. McM-A-343 relaxed the physostigmine-induced contractions but even more contracted the histamine-induced contractions.
These results indicate that McN-A-343-induced contractions are more sensitive to pirenzepine than BCh-induced contractions and infer that the relaxing effect of McN-A-343 result from antagonistic action of McN-A-343 on muscarinic receptor.

목차 (Table of Contents)

• 國文抄錄 = 1
• 緖論 = 3
• 實驗方法 = 4
• 實驗成績 = 6
• 考察 = 15
• 要約 = 18
• 參考文獻 = 20
• 英文抄錄 = 22