Partial agonistic effect of 9-hydroxycorynantheidine on μ-opioid receptor in the guinea-pig ileum
Partial agonistic effect of 9-hydroxycorynantheidine on μ-opioid receptor in the guinea-pig ileum
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DOI：
10.1016/j.lfs.2005.09.030
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发表时间：
2006-04-04
期刊：
影响因子：
6.1
通讯作者：
Horie, S
中科院分区：
文献类型：
--
作者：
Matsumoto, K;Takayama, H;Horie, S
Mitragynine是一种从泰国药用植物Mitragyna speciosa中分离出来的吲哚生物碱，据报道具有阿片激动剂特性。以mitragynine为原料合成了mitragynine的9-去甲基类似物9-hydroxycorynantheidine。9-9-羟基柯楠泰定对电刺激豚鼠回肠收缩有抑制作用，但其最大抑制作用弱于米曲宁，其作用可被纳洛酮拮抗，表明9-羟基柯楠泰定对阿片受体具有部分激动作用。受体结合试验表明，9-羟基紫堇酰泰定对p-阿片受体有很高的亲和力。在豚鼠回肠试验中，纳洛酮以竞争性方式使[D-Ala（2）、N-MePhe（4）、Gly-ol（5）]-脑啡肽（DAMGO）、（5 α，7 α，8 β）-（+）-N-甲基-N-[7-（1-吡咯烷基）-1-氧杂螺[4.5]癸-8-基]-苯乙酰胺（U69593）和9-羟基紫堇酰苯胺的浓度-响应曲线向右偏移。纳洛酮对9-羟基柯楠替啶和DAMGO的pA（2）值非常相似，但对U69593的pA（2）值不同。如两种测定系统所示，9-羟基柯楠替啶的阿片样作用对β-阿片样受体具有选择性。9-羟基柯楠替啶使DAMGO的浓度-反应曲线略微向右移动。用μ-阿片选择性和不可逆拮抗剂β-funaltorexamine hydrochloride（β-FNA）预处理使DAMGO的浓度-反应曲线向右移动，而不影响最大反应。另一方面，β-FNA并不影响9-羟基紫堇泰啶的曲线，但由于缺乏备用受体而降低了最大响应。这些研究表明，9-羟基紫堇泰定对豚鼠回肠中的μ-阿片受体具有部分激动剂性质。(c)2005年爱思唯尔公司All rights reserved.
Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa that is reported to have opioid agonistic properties. The 9-demethyl analogue of mitragynine, 9-hydroxycorynantheidine, is synthesized from mitragynine. 9-Hydroxycorynantheidine inhibited electrically stimulated guinea-pig ileum contraction, but its maximum inhibition was weaker than that of mitragynine and its effect was antagonized by naloxone, suggesting that 9-hydroxycorynantheidine possesses partial agonist properties on opioid receptors. Receptor binding assays revealed that 9-hydroxycorynantheidine has high affinity for p-opioid receptors. In an assay of the guinea-pig ileum, naloxone shifted the concentration-response curves for [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO), (5 alpha,7 alpha,8 beta)-(+)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69593) and 9-hydroxycorynantheidine to the right in a competitive manner. The pA(2) values of naloxone against 9-hydroxycorynantheidine and DAMGO were very similar, but not that against U69593. As indicated by the two assay systems, the opioid effect of 9-hydroxycorynantheidine is selective for the p-opioid receptor. 9-Hydroxycorynantheidine shifted the concentration-response curve for DAMGO slightly to the right. Pretreatment with the mu-opioid selective and irreversible antagonist beta-funaltorexamine hydrochloride (beta-FNA) shifted the concentration-response curve for DAMGO to the right without affecting the maximum response. On the other hand, beta-FNA did not affect the curve for 9-hydroxycorynantheidine, but decreased the maximum response because of the lack of spare receptors. These studies suggest that 9-hydroxycorynantheidine has partial agonist properties on mu-opioid receptors in the guinea-pig ileum. (c) 2005 Elsevier Inc. All rights reserved.