Benyhe S, Szücs M, Borsodi A, Wollemann M
Institute of Biochemistry, Hungarian Academy of Sciences, Szeged.
Life Sci. 1992;51(21):1647-55. doi: 10.1016/0024-3205(92)90309-d.
Stereoselectivity of the binding sites for the specific kappa-opioid agonist [3H]U-69593, a benzeneacetamido based ligand was investigated in membrane suspension prepared from frog and rat brain, as well as guinea pig cerebellum, using the pure chiral forms of different unlabelled opiates. The ligand binding sites showed stereospecificity with at least three orders of magnitude differences in the affinities (measured as Ki values) of the opioid stereoisomer pairs both in rat and guinea pig membrane fractions. However, in frog brain membranes there was no substantial difference in potencies of the (-) and (+) isomers competing for the [3H]U-69593 binding sites. Another type of the kappa-site preferring opioid ligand, [3H]ethylketocyclazocine, a benzomorphan derivative was able to discriminate between (-) and (+) forms of the same compounds even in frog brain membrane preparation. Our data concerning binding profile of [3H]U-69593 in frog brain membranes are consistent with the observation that kappa opioid binding sites in frog (Rana esculenta) brain differ from those kappa-sites found in mammalian brains.
使用不同未标记阿片类药物的纯手性形式，在由青蛙和大鼠脑以及豚鼠小脑制备的膜悬浮液中，研究了基于苯乙酰胺的特异性κ-阿片受体激动剂[3H]U-69593结合位点的立体选择性。在大鼠和豚鼠膜组分中，配体结合位点表现出立体特异性，阿片类立体异构体对的亲和力（以Ki值衡量）至少相差三个数量级。然而，在青蛙脑膜中，（-）和（+）异构体竞争[3H]U-69593结合位点的效力没有实质性差异。另一种偏向κ-位点的阿片类配体[3H]乙基酮环唑新，一种苯并吗啡烷衍生物，即使在青蛙脑膜制备中也能够区分相同化合物的（-）和（+）形式。我们关于[3H]U-69593在青蛙脑膜中结合情况的数据与青蛙（食用蛙）脑中κ-阿片受体结合位点与哺乳动物脑中发现的κ-位点不同这一观察结果一致。
