Abstracts (pages 151-155)
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- 关键词：Adrenergic receptor ; Antagonist ; Inverse agonist ; G protein ; coupled receptors ; Stable transfection ; 1 ; receptor ; 2 ; receptor ; 3 ; receptor
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：2004
- 出版时间：March 2004
- 年：2004
- 卷：369
- 页码：151-155
- 全文大小：1,364 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology
Neurosciences - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1912
文摘
Although many 1-receptor antagonists and 2-receptor agonists have been used in pharmacotherapy for many years their pharmacological properties at all three known subtypes of -adrenergic receptors are not always well characterized. The aim of this study was, therefore, to provide comparative binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol, fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and antagonists (propranolol, alprenolol, atenolol, metoprolol, bisoprolol, carvedilol, pindolol, BRL 37344, CGP 20712, SR 59230A, CGP 12177, ICI 118551) at all three subtypes of human -adrenergic receptors in an identical cellular background. We generated Chinese hamster ovary (CHO) cells stably expressing the three -adrenergic receptor subtypes at comparable levels. We characterized these receptor subtypes and analyzed the affinity of routinely used drugs as well as experimental compounds in competition binding studies, using the non-selective antagonist 125I-cyanopindolol as a radioligand. Furthermore, we analyzed the -receptor-mediated adenylyl cyclase activity in isolated membranes from these cell lines. The results from our experiments show that all compounds exhibit distinct patterns of selectivity and activity at the three -receptor subtypes. In particular, a number of 2- or 3-receptor agonists that are inverse agonists at the other subtypes were identified. In addition, 1-receptor antagonists with agonistic activity at 2- and 3-receptors were found. These specific mixtures of agonism, antagonism, and inverse agonism at different subtypes may have important implications for the therapeutic use of the respective compounds.