Koike K, Hagiwara H, Takayanagi I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Can J Physiol Pharmacol. 1991 Jul;69(7):951-7. doi: 10.1139/y91-144.
The stereoselectivities of beta-adrenergic partial agonists for the high affinity binding site of beta-adrenoceptors in the rabbit ciliary body and the guinea-pig taenia caeci were studied. The pA2 values of the S-(-)-isomers of befunolol and carteolol against S-(-)-isoprenaline, which were calculated from the shift of each concentration - response curve in increasing cyclic AMP levels, were significantly larger than those of the R-(+)-isomers in the guinea-pig taenia caeci, while the pA2 values of the S-(-)-isomers were not significantly larger than those of the R-(+)-isomers in the rabbit ciliary body. The pK1 values determined from the binding experiments were in good agreement with the pA2 values from the increases in cyclic AMP levels. These results suggest that the high affinity binding site of beta-adrenoceptors in the guinea-pig taenia caeci may be able to discriminate stereoselectively between the R-(+)- and S-(-)-isomers, while in the rabbit ciliary body there is no stereo-selectivity between the two enantiomers.
研究了β-肾上腺素能部分激动剂对兔睫状体和豚鼠盲肠带中β-肾上腺素能受体高亲和力结合位点的立体选择性。从增加环磷酸腺苷水平时各浓度-反应曲线的位移计算得出的倍他洛尔和卡替洛尔的S-(-)-异构体对S-(-)-异丙肾上腺素的pA2值，在豚鼠盲肠带中显著大于R-(+)-异构体的pA2值，而在兔睫状体中S-(-)-异构体的pA2值并不显著大于R-(+)-异构体的pA2值。从结合实验确定的pK1值与环磷酸腺苷水平升高时的pA2值高度一致。这些结果表明，豚鼠盲肠带中β-肾上腺素能受体的高亲和力结合位点可能能够立体选择性地区分R-(+)-和S-(-)-异构体，而在兔睫状体中这两种对映体之间不存在立体选择性。
