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首页> 外文期刊>The European Journal of Neuroscience >Binding characteristics of (3H)14-methoxymetopon, a high affinity mu-opioid receptor agonist.
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Binding characteristics of (3H)14-methoxymetopon, a high affinity mu-opioid receptor agonist.

机译：高亲和力的μ-阿片受体激动剂（3H）14-甲氧基甲酮的结合特性。

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摘要

The highly potent micro -opioid receptor agonist 14-methoxymetopon (4,5alpha-epoxy-3-hydroxy-14beta-methoxy-5beta,17-dimethylmorphinan-6-one) was prepared in tritium labelled form by a catalytic dehalogenation method resulting in a specific radioactivity of 15.9 Ci/mmol. Opioid binding characteristics of [3H]14-methoxymetopon were determined using radioligand binding assay in rat brain membranes. [3H]14-Methoxymetopon specifically labelled a single class of opioid sites with affinity in low subnanomolar range (Ki = 0.43 nm) and maximal number of binding sites of 314 fmol/mg protein. Binding of [3H]14-methoxymetopon was inhibited by ligands selective for the micro -opioid receptor with high potency, while selective kappa-opioids and delta-opioids were weaker inhibitors. 14-Methoxymetopon increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding with an EC50 of 70.9 nm, thus, providing evidence for the agonist character of this ligand. The increase of [35S]GTPgammaS binding was inhibited by naloxone and selective micro -opioid antagonists, indicating a micro -opioid receptor-mediated action. [3H]14-Methoxymetopon is one of the few nonpeptide mu-opioid receptor agonists available in radiolabelled form up to now. Due to its high affinity and selectivity, high stability and extremely low nonspecific binding (<10%), this radioligand would be an important and useful tool in probing mu-opioid receptor mechanisms, as well as to promote a further understanding of the opioid system at the cellular and molecular level.
机译：用tri标记的形式通过催化脱卤法制备了高效的微阿片受体激动剂14-甲氧基美托品（4,5α-环氧-3-羟基-14β-甲氧基-5β，17-二甲基吗啡喃-6-一）比放射性为15.9 Ci / mmol。使用放射性配体结合测定法在大鼠脑膜中测定[3H] 14-甲氧基美托普的阿片样物质结合特征。 [3H] 14-甲氧基美通酮以低亚纳摩尔范围（Ki = 0.43 nm）和314 fmol / mg蛋白的最大结合位点特异性标记了单类阿片样物质位点。 [3H] 14-甲氧基美通体的结合被对微阿片受体具有选择性的配体抑制，且效力高，而选择性κ-阿片和δ-阿片类是较弱的抑制剂。 14-甲氧基美通酮增加鸟苷5'-O-（3- [35S]硫代）-三磷酸酯（[35S] GTPgammaS）的结合，EC50为70.9 nm，因此为该配体的激动剂特性提供了证据。 [35S]GTPγS结合的增加被纳洛酮和选择性微阿片类拮抗剂抑制，表明微阿片受体介导的作用。迄今为止，[3H] 14-甲氧基美通酮是放射性标记形式的少数非肽类μ阿片受体激动剂之一。由于其高亲和力和选择性，高稳定性和极低的非特异性结合（<10％），该放射性配体将成为探测μ阿片受体机制的重要和有用工具，并促进对阿片系统的进一步了解在细胞和分子水平。

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