Seya K, Miki I, Murata K, Junke H, Motomura S, Araki T, Itoyama Y, Oshima Y
Department of Pharmacology, Hirosaki University School of Medicine, Japan.
J Pharm Pharmacol. 1998 Jul;50(7):803-7. doi: 10.1111/j.2042-7158.1998.tb07143.x.
We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0.1-1 microM) had no effect on the contraction of the ileum induced by acetylcholine at 10 microM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0.1-10 microM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 microM. From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6.6. The contraction of the ileum induced by 10 microM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine receptors, was concentration-dependently suppressed by 10 nM-10 microM pteleprenine. In contrast, 0.1-10 microM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.
我们研究了喹啉生物碱白屈菜红碱对豚鼠回肠收缩反应和犬左心房变力性反应的药理特性。尽管白屈菜红碱（0.1 - 1微摩尔）对10微摩尔乙酰胆碱诱导的回肠收缩没有影响，但它能显著抑制乙酰胆碱诱导的回肠收缩。白屈菜红碱（0.1 - 10微摩尔）以浓度依赖性方式降低尼古丁诱导的回肠收缩，即使在10微摩尔浓度下也没有最大舒张作用。通过Schild分析，发现白屈菜红碱对豚鼠回肠的pA2为6.6。10 nM - 10微摩尔的白屈菜红碱浓度依赖性地抑制了由10微摩尔1,1 - 二甲基 - 4 - 苯基哌嗪鎓（一种烟碱型乙酰胆碱受体的特异性激动剂）诱导的回肠收缩。相比之下，0.1 - 10微摩尔的白屈菜红碱并不拮抗乙酰胆碱和尼古丁诱导的犬左心房负性变力性收缩反应。这些结果表明，白屈菜红碱对豚鼠回肠中的烟碱型乙酰胆碱受体有抑制作用，但对犬左心房中的该受体没有抑制作用。我们的研究结果还表明，白屈菜红碱可能是一种新型的烟碱受体拮抗剂先导化合物。
