Pteropodine and isopteropodine positively modulate the function of rat muscarinic M1 and 5-HT2 receptors expressed in Xenopus oocyte
Pteropodine and isopteropodine positively modulate the function of rat muscarinic M1 and 5-HT2 receptors expressed in Xenopus oocyte
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DOI：
10.1016/s0014-2999(02)01608-4
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发表时间：
2002-05-24
影响因子：
5
通讯作者：
Watanabe, H
中科院分区：
文献类型：
--
作者：
Kang, TH;Matsumoto, K;Watanabe, H
翼龙碱和异翼龙碱是毛毛钩藤中异育亨碱型氧吲哚类生物碱成分。一种秘鲁药用植物，被称为猫爪。本研究在翻译大鼠皮质总RNA的爪蟾卵母细胞中，研究了这些生物碱对G蛋白偶联毒蕈碱M-1乙酰胆碱和5-HT2受体刺激引起的Ca2+激活Cl-电流功能的影响。翼龙柏碱和异翼龙柏碱（1- 30mum）不能自行诱导膜电流。然而，这些生物碱以浓度依赖性和可逆性的方式显著增强乙酰胆碱和5-羟多巴胺（5-HT）引起的电流反应，在30ma时效果最大。翼龙桃碱和异翼龙桃碱对乙酰胆碱的反应分别增加2.7倍和3.3倍，EC50分别为9.52和9.92 muM；对5-羟色胺的反应分别增加2.4倍和2.5倍，EC50分别为13.5和14.5 muM。相比之下，在注射了大鼠小脑或脊髓总RNA的卵母细胞中，生物碱对谷氨酸受体（1和5）（mGlu(15)）受体介导的代谢电流反应或n -甲基- d -天冬氨酸介导的嗜离子反应均无影响。Kainic酸或甘氨酸。紫檀碱和异紫檀碱（10 muM）显著降低了乙酰胆碱和5-HT引起的电流反应的EC50值，但对乙酰胆碱和5-HT引起的最大电流反应没有影响。另一方面，翼蟾碱的立体异构体mitraphylline不能调节乙酰胆碱和5- ht诱导的反应。这些结果表明，翼莨菪碱和异翼莨菪碱是毒蕈碱M和5-HT受体的正向调节剂。(C) 2002 Elsevier Science b.v.版权所有
Pteropodine and isopteropodine are heteroyohimbine-type oxindole alkaloid components of Uncaria tomentosa (Willd.) DC, a Peruvian medicinal plant known as cat's claw. In this study, the effects of these alkaloids on the function of Ca2+-activated Cl- currents evoked by stimulation of G protein-coupled muscarinic M-1 acetylcholine and 5-HT2 receptors were studied in Xenopus oocytes in which rat cortex total RNA was translated. Pteropodine and isopteropodine (1-30 muM) failed to induce membrane current by themselves. However, these alkaloids markedly enhanced the current responses evoked by both acetylcholine and 5-hydroxyhyptamine (5-HT) in a concentration-dependent and reversible manner with the maximal effects at 30 muM. Pteropodine and isopteropodine produced 2.7- and 3.3-fold increases in the acetylcholine response with EC50 values of 9.52 and 9.92 muM, respectively, and 2.4- and 2.5-fold increases in the 5-HT response with EC50 values of 13.5 and 14.5 muM, respectively. In contrast, in oocytes injected with total RNA from the rat cerebellum or spinal cord, neither alkaloid had an effect on the metabotropic current responses mediated by glutamate receptor(1 and 5) (mGlu(1 5)) receptors or ionotropic responses mediated by N-methyl-D-aspartate. kainic acid or glycine. Pteropodine and isopteropodine (10 muM) significantly reduced the EC50 values of acetylcholine and 5-HT that elicited current responses, but had no effect on the maximal current responses elicited by acetylcholine and 5-HT. On the other hand, mitraphylline, a stereoisomer of pteropodine, failed to modulate acetylcholine- and 5-HT-induced responses. These results suggest that pteropodine and isopteropodine act as positive modulators of muscarinic M, and 5-HT, receptors. (C) 2002 Elsevier Science B.V All rights reserved.