来自加勒比海柳珊瑚的二萜类化合物可作为烟碱型乙酰胆碱受体的非竞争性抑制剂。
Diterpenoids from Caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor.
作者信息
Eterović V A, Hann R M, Ferchmin P A, Rodriguez A D, Li L, Lee Y H, McNamee M G
机构信息
Department of Biochemistry, Universidad Central del Caribe, Bayamón, Puerto Rico 00960.
出版信息
Cell Mol Neurobiol. 1993 Apr;13(2):99-110. doi: 10.1007/BF00735367.
Abstract
- Three cyclic diterpenoids isolated from gorgonians of the Eunicea genus and characterized as eupalmerin acetate (EUAC), 12,13-bisepieupalmerin (BEEP), and eunicin (EUNI) were found to be pharmacologically active on the nicotinic acetylcholine receptor (AChR). 2. The receptor from the BC3H-1 muscle cell line was expressed in Xenopus laevis oocytes and studied with a two-electrode voltage clamp apparatus. 3. All three compounds reversibly inhibited ACh-induced currents, with IC50's from 6 to 35 microM. ACh dose-response curves suggested that his inhibition was noncompetitive. The cembranoids also increased the rate of receptor desensitization. 4. Radioligand-binding studies using AChR-rich membranes from Torpedo electric organ indicated that all three cembranoids inhibited high-affinity [3H]phencyclidine binding, with IC50's of 0.8, 11.6, and 63.8 microM for EUNI, EUAC, and BEEP, respectively. The cembranoids at a 100 microM concentration did not inhibit [alpha-125I]bungarotoxin binding to either membrane-bound or solubilized AChR. 5. It is concluded that these compounds act as noncompetitive inhibitors of peripheral AChR.
摘要
- 从Eunicea属柳珊瑚中分离出的三种环状二萜类化合物，分别鉴定为乙酸尤帕麦灵（EUAC）、12,13-双表尤帕麦灵（BEEP）和尤尼辛（EUNI），被发现对烟碱型乙酰胆碱受体（AChR）具有药理活性。2. BC3H-1肌肉细胞系的受体在非洲爪蟾卵母细胞中表达，并用双电极电压钳装置进行研究。3. 所有这三种化合物均可逆地抑制乙酰胆碱诱导的电流，IC50值在6至35微摩尔之间。乙酰胆碱剂量反应曲线表明这种抑制是非竞争性的。这些西松烷类化合物还提高了受体脱敏的速率。4. 使用电鳐电器官富含AChR的膜进行的放射性配体结合研究表明，所有这三种西松烷类化合物均抑制高亲和力的[3H]苯环利定结合，EUNI、EUAC和BEEP的IC50值分别为0.8、11.6和63.8微摩尔。100微摩尔浓度的西松烷类化合物不抑制[α-125I]银环蛇毒素与膜结合或可溶的AChR的结合。5. 得出的结论是，这些化合物作为外周AChR的非竞争性抑制剂起作用。
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