布尼洛尔对β1-和β2-肾上腺素能受体以及5HT1B受体的选择性：通过双相Scatchard图和使用125I-碘氰吲哚洛尔及3H-CGP12177的双相置换曲线分析进行评估。

Selectivity of bunitrolol for beta 1- and beta 2-adrenergic receptors and 5HT1B-receptors: assessment by biphasic Scatchard plots and biphasic displacement curve analysis with 125I-iodocyanopindolol and 3H-CGP12177.

作者信息

Tsuchihashi H, Nagotomo T, Imai S

机构信息

Department of Pharmacology, Niigata College of Pharmacy, Japan.

出版信息

Jpn J Pharmacol. 1989 Jun;50(2):93-100. doi: 10.1254/jjp.50.93.

DOI:10.1254/jjp.50.93

PMID:2570175

Abstract

The preference by bunitrolol for beta 1- and beta 2-adrenoceptors of the rat brain, heart and/or lung was assessed by the radioligand binding assay method with 125I-iodocyanopindolol (125I-ICYP) or 3H-CGP12177. Scatchard plots of 125I-ICYP binding in the presence of bunitrolol were found to be non-linear. The inhibition constants (Ki) of bunitrolol for high (beta 2-) and low affinity sites (beta 1-) were: 0.42 +/- 0.16 nM for beta 1 and 3.55 +/- 1.61 nM for beta 2 (beta 1 greater than beta 2), respectively. Displacement experiments conducted with the preparations of the rat brain using 125I-ICYP or with the preparations of the rat heart using 3H-CGP12177 yielded Ki values for bunitrolol of 0.53 +/- 0.20 (beta 1) and 2.37 +/- 0.78 (beta 2) nM for 125I-ICYP binding and 2.01 +/- 0.38 (beta 1) and 12.67 +/- 6.54 (beta 2) nM for 3H-CGP12177 binding. In addition, the Ki value for 5HT1B-receptors assessed in displacement experiments conducted with 125I-ICYP in the presence of 30 microM I-metoprolol in the rat brain was 10.54 +/- 5.92 nM. Thus, bunitrolol is a beta 1-selective antagonist.

摘要

采用放射性配体结合分析法，使用125I-碘氰吲哚洛尔（125I-ICYP）或3H-CGP12177评估布尼洛尔对大鼠脑、心脏和/或肺中β1-和β2-肾上腺素能受体的亲和力。在布尼洛尔存在的情况下，125I-ICYP结合的Scatchard图呈非线性。布尼洛尔对高亲和力位点（β2-）和低亲和力位点（β1-）的抑制常数（Ki）分别为：β1为0.42±0.16 nM，β2为3.55±1.61 nM（β1大于β2）。使用125I-ICYP对大鼠脑匀浆或使用3H-CGP12177对大鼠心脏匀浆进行的置换实验中，布尼洛尔对125I-ICYP结合的Ki值为β1为0.53±0.20 nM，β2为2.37±0.78 nM；对3H-CGP12177结合的Ki值为β1为2.01±0.38 nM，β2为12.67±6.54 nM。此外，在大鼠脑内30 μM I-美托洛尔存在的情况下，使用125I-ICYP进行置换实验评估的5HT1B受体的Ki值为10.54±5.92 nM。因此，布尼洛尔是一种β1选择性拮抗剂。